Question about non-varicose ADH. Young patient, with no previous history, who after taking NSAIDs presents bleeding with hemodynamic instability requiring transfusion.  Answer 1 is not in accordance with what has been said, this is an unstable patient who has bled a lot, who has a Forrest IIa ulcer with a high risk of rebleeding. Answer 2 speaks of somatostatin, which is used for bleeding due to portal hypertension. 4 will only be considered if bleeding is not controlled endoscopically. Between 3 and 5, since there is a high risk of bleeding, endoscopic therapy is recommended, preferably with 2 techniques, so the correct one would be 5.

Question about non-varicose ADH. Young patient, with no previous history, who after taking NSAIDs presents bleeding with hemodynamic instability requiring transfusion. Answer 1 is [HIDDEN], this is an unstable patient who has bled a lot, who has a Forrest IIa ulcer with a high risk of rebleeding. Answer 2 speaks of somatostatin, which is used for bleeding due to portal hypertension. 4 will only be considered if bleeding is not controlled endoscopically. Between 3 and 5, since there is a high risk of bleeding, endoscopic therapy is recommended, preferably with 2 techniques, so [HIDDEN].

A 43-year-old man with no diseases of interest comes to the emergency department for 4 melaenic stools in the last 12 hours. He refers taking NSAIDs in previous days. Physical examination revealed pale skin and mucous membranes. BP 95/65 and HR 110 bpm. The abdomen is not painful and rectal examination shows melenic stools. The CBC shows a Hb of 8.1 gr/dl. After infusion of saline and the start of red blood cell concentrate transfusion, the BP was 120/85 and HR 90 bpm. An endoscopy was performed in which clots were found in the stomach and a 2 cm ulcer in the gastric antrum with fibrin background and a small grayish-white protrusion of 3 mm in the center of the ulcer (visible platelet thrombus vessel). What do you think is the most correct approach?

Since the patient is young, with no associated diseases and the ulcer has stopped bleeding, he can be discharged early with treatment with a PPI and H. Pylori eradication.

Remove the endoscope, place nasogastric tube for continuous aspiration and initiate treatment with a PPI and somatostatin.

Take biopsy for H. Pylori, remove the endoscope taking care not to dislodge the platelet thrombus and continue pharmacological treatment with i.v. PPI.

Consultation to the surgical service to consider urgent surgical treatment.

Endoscopic treatment by injection of adrenaline into the ulcer and placement of clips (metal staples) followed by i.v. administration of PPI.

[Diagnosis and treatment of bleeding peptic ulcer: our experience].

Bleeding peptic ulcer (PU) is the commonest cause of an acute upper gastrointestinal bleed. Aim of this study was to present our data regard the management of acute bleeding from PU during urgent endoscopy (examination performed in 2-6 h by the call). This study is based on an observational retrospective protocol. Records of 259 consecutive patients with PU (92 F, 167 M; median age 71.5 years; range: 19-100 years), attending our GI Unit from February 1st 2004 to July 31st 2007, were analyzed. Out of 259 patients with PU, 170 (65.6%) were treated with endoscopic hemostasis followed by medical therapy (PPI 80 mg bolus within 12 h of endoscopy followed by 8 mg/for 72 h and then an oral PPI , 40 mg once daily for 30 days), while 89 (34.4%) patients received only medical therapy (PPI, 40 mg once daily for 30 days). All ulcerative lesions with endoscopic stigmata of acute bleeding, visible vessels or adherent clot (Forrest Ia-IIb) were treated during the gastroscopy. The endoscopic procedures used were: injection of 1:10000 adrenaline (about 10 mL) around the bleeding lesion in 93 cases (55%); injection therapy and thermal method (argon plasma coagulation) in 53 cases (31%); injection therapy and mechanical method (metallic clips) in 20 cases (12%); only mechanical method (metallic clips) in 4 cases (2%). Endoscopic hemostasis was achieved in 251 pts (97%), while 17 pts (6.5%) required second endoscopy for rebleeding. Three patients (1.16%) required immediate surgery for failure of primary endoscopic hemostasis. The mortality within 30 days from the bleeding episode was 3.9% (10 pts). The treatment of this condition has made important progress since the introduction of emergency endoscopy and endoscopic techniques for hemostasis. The application of specific protocols, significantly decreases rebleeding and the need for surgery, whereas mortality is still high. Our data are in keeping with previous studies of the literature.

Peptic ulcer disease

Early endoscopic therapy can help to stop bleeding by using cautery, endoclip, or epinephrine injection. Treatment is indicated if there is active bleeding in the stomach, visible vessels, or an adherent clot. Endoscopy is also helpful in identifying people who are suitable for hospital discharge. Prokinetic agents such as erythromycin and metoclopramide can be given before endoscopy to improve endoscopic view. Either high- or low-dose PPIs are equally effective in reducing bleeding after endoscopy. High-dose intravenous PPI is defined as a bolus dose of 80 mg followed by an infusion of 8 mg per hour for 72 hours—in other words, the continuous infusion of PPI of greater than 192 mg per day. Intravenous PPI can be changed to oral once there is no high risk of rebleeding from peptic ulcer.

The efficacy of PPI after endoscopic hemostasis in patients with bleeding peptic ulcer and role of Helicobacter pylori.

Nowadays PPI present cornerstone in the medical therapy of bleeding peptic ulcer. Controlled pantoprazole data in peptic ulcer bleeding are few. To compare the effect of intravenous (iv) pantoprazole (PPI) with iv ranitidine (H2RA) for bleeding peptic ulcers after endoscopic therapy. After endoscopic haemostasis, 122 patients were randomized to PPI 80 mg + 8 mg/h or H2RA 50 mg + 13 mg/h, both for 72 h and to continue with oral equivalent dose of these medicaments. Patients underwent second-look endoscopy on day 3 or earlier, if clinically indicated. The primary endpoint measure was rebleeding before discharge and <14 days of enrollment. Secondary endpoint measures included number of surgeries performed, volume of blood transfusion, mortality rate and hospital stay. All data were statistically analyzed and a value of 0.05 or less was considered to indicate statistical significance. In the group who were treated with PPI, re-bleeding rate was evidenced in 5 patients (8.33%) and in the groups who were treated with H2RA, re-bleeding rate was found in 9 patients (14.5%) with RR 0.27 and CI 0.12-0.60 and P < 0.05. The volume of transfused blood was lower in the group treated with PPI compared to the group treated with H2RA (930 ml vs. 1540 ml and P < 0.05). In this study there was not statistically significant difference in the hospital stay 15.00 vs. 17.80% (9 vs. 11 patients and P> 0.05), the need for surgical intervention 5.00 vs. 6.45% (3 vs. 4 patients and P= 1.00) and the mortality rate 1.66 vs. 3.22% (1 vs. 2 patients and P > 0.05). A high-dose pantoprazole infusion is more effective than a ranitidine infusion for prevention of re-bleeding after endoscopic epinephrine injection in patients with peptic ulcers and active bleeding or non-bleeding visible vessels (P < 0.05). In all bleeding peptic ulcer patients is needed to make the eradication of H. pylori infection with the aim to prevent re-bleeding in long term.

[Peptic ulcer disease and H. pylori gastritis: key advances in clinical management].

Helicobacter pylori (H. pylori) gastritis and non-steroidal anti-inflammatory drug (NSAID) intake are the most important risk factors for peptic ulcer disease (PUD) and ulcer bleeding. H. pylori infection was shown to increase the risk of ulcer bleeding in patients with PUD who are taking NSAID, aspirin, or another antiplatelet drug. H. pylori-positive patients on combined platelet aggregation inhibition are at the highest risk of bleeding. Evidence-based interdisciplinary treatment recommendations for the safe use of NSAID have been released. For patients with a moderate risk of PUD, the combination of NSAID and a proton pump inhibitor (PPI) or a monotherapy with a selective cyclooxygenase-2 (COX-2) inhibitor is recommended, whereas patients with a high risk of bleeding should receive a combination of a selective COX-2 inhibitor and a PPI. According to a recent randomized trial, hemodynamically stable patients with signs of upper gastrointestinal bleeding and an increased risk of death (Glasgow-Blatchford Score ≥ 12) undergoing endoscopy 6-24 after consultation do not have any disadvantage in terms of 30-day mortality compared to patients receiving endoscopy within 6 hours. After successful endoscopic hemostasis, additional prophylactic angiographic embolization does not reduce the risk of recurrent bleeding. Successful H. pylori eradication reduces the risk of developing gastric cancer (GC) in first-degree relatives of patients with GC by 73 %. In patients with successful endoscopic treatment of early GC, H. pylori testing with subsequent eradication also halves the rate of metachronous GC. Clarithromycin-based triple therapy for H. pylori eradication shows a decreasing effectiveness due to increasing antibiotic resistance, especially against macrolides. Accordingly, bismuth-containing quadruple therapy is widely recommended as the standard empiric first-line therapy.

Proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding.

Peptic ulcer bleeding is a common and potentially fatal condition. For patients with bleeding peptic ulcers that display major endoscopic stigmata of recent hemorrhage, a combination of endoscopic and pharmacologic therapy is the current standard management. To show our experience with management of peptic ulcer bleeding. Patients who presented with gastrointestinal bleeding caused by peptic ulcer or recent history (< 24 h before presentation) of hematemesis and/or melena admitted to our hospital emergency departments, and patients whose ulcer hemorrhage started after hospitalization for an unrelated medical or surgical condition. Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or endoscopic hemoclips, and randomized to receive intravenous pantoprasole according to the continuous regimen (dose of 5 x 40 mg in continuous infusion of 8 mg/h for 72 h) or the standard regimen (40 mg bolus of PPI twice daily for 3 days). After the infusion, all patients were given 40 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as discovered by the repeated endoscopy. Bleeding recurred in 5 of 34 patients (14.7%) receiving the intensive regimen, and in 8 of 35 (22.8%) patients receiving the standard regimen. Hemoglobin (g/l) rate in standard regimen group was 93.5 +/- 23.8, and in intensive regimen group 106.6 +/- 22.4 (P = 0.042). Mean units of blood transfused for all patients in group were 71.8 +/- 45.8 in the intensive and 45.3 +/- 50.2 in the standard regimen group (P = 0.0257). The duration of hospital stay was 6.4 +/- 2.8 in standard group and 5.8 +/- 2.8 in the intensive group (P = 0.40). In patients with bleeding peptic ulcers with successful endoscopic hemostasis the standard PPI regimen had advantage on transfusion requirements, but no advantage with respect to in-hospital rates of rebleeding rates, need for surgery, length of hospital stay, or death, which corresponds with recent studies.

High-dose omeprazole infusion compared with scheduled second-look endoscopy for prevention of peptic ulcer rebleeding: a randomized controlled trial.

Previous studies have shown that both scheduled second-look endoscopy and high-dose continuous omeprazole infusion are effective in preventing peptic ulcer rebleeding. The aim of this noninferiority trial was to compare the efficacy of these two strategies for the prevention of rebleeding following primary endoscopic hemostasis. Consecutive patients who received endoscopic treatment for bleeding peptic ulcers (actively bleeding, with nonbleeding visible vessels) were randomized to two treatment groups following hemostasis. One group (second-look endoscopy group) received the proton pump inhibitor (PPI) omeprazole as an intravenous bolus every 12 hours for 72 hours and a second endoscopy within 16 - 24 hours with retreatment for persistent stigmata of bleeding. The other group (PPI infusion group) received continuous high-dose omeprazole infusion for 72 hours. Patients who developed rebleeding underwent surgery if repeat endoscopic therapy failed. The primary outcome was the rebleeding rate within 30 days after initial hemostasis. The margin for noninferiority was set at 5 %. A total of 153 patients were randomized to the PPI infusion group and 152 to the second-look endoscopy group. Rebleeding occurred within 30 days in 10 patients (6.5 %) in the PPI infusion group and in 12 patients (7.9 %) in the second-look endoscopy group (P = 0.646). Surgery was required for rebleeding in six patients from the PPI infusion group and three patients in the second-look endoscopy group (P = 0.32). Intensive care unit stay, transfusion requirements, and mortality were not different between the groups. Patients in the second-look endoscopy group were discharged 1 day earlier than those in the PPI infusion group (P < 0.001). After endoscopic hemostasis, high-dose PPI infusion was not inferior to second-look endoscopy with bolus PPI in preventing peptic ulcer rebleeding. ClinicalTrials.gov (NCT: 00164931).

Oral proton pump inhibitors are as effective as endoscopic treatment for bleeding peptic ulcer: a prospective, randomized, controlled trial.

In managing patients with bleeding peptic ulcers, it has been reported that pharmacologic treatment can be an alternative to endoscopic treatment. We compared the hemostasis rates of the endoscopic treatment, hemoclipping, and the pharmacologic treatment, oral proton pump inhibitors (PPIs), in bleeding peptic ulcer. A randomized prospective study was performed on 129 bleeding peptic ulcer patients with hematemesis or melena. Sixty-two patients were treated by endoscopic hemoclipping and subsequently H(2) receptor antagonists were injected intravenously (hemoclipping group), and 67 patients were treated with an oral PPI without endoscopic treatment (PPI group). The 24-hr gastric pH test was performed sequentially following the treatment. The initial hemostasis rate of the hemoclipping group was 93.5% (58/62) and the rebleeding rate was 6.9% (4/58), and the hemostasis rate of the PPI group was 92.5% (62/67) and the rebleeding rate was 7.5% (5/67), which were not different. The 24-hr gastric pH was 4.54+/-2.56 in the hemoclipping group and 5.97+/-1.30 in the PPI group (P<0.037). In the bleeding peptic ulcer patients, the hemostasis rate with the oral administration of PPIs was not different from that with the endoscopic hemoclipping treatment.

Management of bleeding gastroduodenal ulcers.

A multidisciplinary group of Danish experts developed this guideline on management of bleeding gastroduodenal ulcers. Sources of data included published studies up to March 2011. Quality of evidence and strength of recommendations have been graded. The guideline was approved by the Danish Society of Gastroenterology and Hepatology September 4, 2011. Recommendations emphasize the importance of early and efficient resuscitation. Endoscopy should generally be performed within 24 hours, reducing operation rate, rebleeding rate and duration of in-patient stay. When serious ulcer bleeding is suspected and blood found in gastric aspirate, endoscopy within 12 hours will result in faster discharge and reduced need for transfusions. Endoscopic hemostasis remains indicated for high-risk lesions. Clips, thermocoagulation, and epinephrine injection are effective in achieving endoscopic hemostasis. Use of endoscopic monotherapy with epinephrine injection is not recommended. Intravenous high-dose proton pump inhibitor (PPI) therapy for 72 hours after successful endoscopic hemostasis is recommended as it decreases both rebleeding rate and mortality in patients with high-risk stigmata. Although selected patients can be discharged promptly after endoscopy, high-risk patients should be hospitalized for at least 3 days after endoscopic hemostasis. Patients with peptic ulcer bleeding who require secondary cardiovascular prophylaxis should start receiving acetylsalicylic acid (ASA) again as soon as cardiovascular risks outweigh gastrointestinal risks. Patients in need of continued treatment with ASA or a nonsteroidal anti-inflammatory drug should be put on prophylactic treatment with PPI at standard dosage. The combination of 75mg ASA and PPI should be preferred to monotherapy with clopidogrel in patients needing anti-platelet therapy on the basis of indications other than coronary stents.

[Guidelines of treatment for bleeding peptic ulcer disease].

Peptic ulcer (PU) bleeding is the main cause of non-variceal gastrointestinal bleeding. Negative outcomes include re-bleeding and death, and many of the deaths are associated with decompensation of coexisting medical conditions precipitated by acute bleeding event. Accurate analysis of risk for clinical features can help physician to decide treatment modality. Endoscopy can detect bleeding stigmata and perform therapeutic hemostasis. Proton pump inhibitor (PPI) compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in upper gastrointestinal (UGI) bleeding significantly reduces the proportion of patients with stigmata of recent hemorrhage (SRH) at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with endoscopic hemostasis for those with major SRH, is likely to be the most cost-effective. The treatment of H. pylori infection was found to be more effective than anti-secretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone and eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies to prevent ulcer bleeding among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective treatment. This review focuses specifically on the current treatment of patients with acute bleeding from a peptic ulcer.

Clinical practice and evidence in endoscopic treatment of bleeding peptic gastroduodenal ulcer.

To investigate treatment practice in non-variceal upper gastrointestinal bleeding (NVUGIB) caused by gastroduodenal ulcer and how it adheres to the best evidence as documented in randomized studies and meta-analyses. The literature was surveyed to identify appropriate practices, and a structured multiple choice questionnaire developed and mailed to all departments in Denmark treating UGIB. All 42 departments responded. All had therapeutic gastroscopes and equipment necessary for endoscopic haemostasis; 90% of departments had written guidelines. Adjuvant pharmacologic treatment included tranexamic acid in 38%. Proton-pump inhibitors (PPIs) were used by all departments, with 29% starting prior to endoscopic treatment. Eight departments (19%) used continuous PPI infusion, three of them starting with a bolus dose. In 50% of departments an anaesthesiologist was always present regardless of whether endotracheal intubation (routinely used by 10%) was used or not. Ten percent did not treat Forrest IIa and IIb ulcers, while IIc ulcers were treated by 36%. In 10% of departments clots were never removed, while in 2/3 attempts were made to remove resistant clots by mechanic means. Seven departments (17%) used monotherapy with epinephrine, while 59% always used dual therapy; 19% injected less than 10 ml. In rebleeding, 92% attempted endoscopic treatment before surgery, and used epinephrine in 79% of cases, while the remainder used epinephrine or polidocanol at the discretion of the endoscopist. Two out of three departments used high-dependency or intensive-care units for surveillance. Seventeen percent applied scheduled second-look gastroscopy. Practice is variable, even in areas with established evidence based on randomized controlled studies, such as dosage and way of administration and duration of PPI treatment, injection treatment used as monotherapy and the volume used, including ulcers with clots for treatment, and the use of scheduled second-look endoscopy. Since the rebleeding rate has remained unchanged for decades, and rebleeding implies increased surgery and mortality rates, appropriate practices must be promoted in order to improve results. Development and implementation of national guidelines may facilitate the process.

Peptic ulcer disease

NSAIDs induced ulcers NSAID-associated ulcers heal in 6 to 8 weeks provided the NSAIDs are withdrawn with the introduction of proton pump inhibitors (PPI). Bleeding For those with bleeding peptic ulcers, fluid replacement with crystalloids is sometimes given to maintain volume in the blood vessels. Maintaining haemoglobin at greater than 7 g/dL (70 g/L) through restrictive blood transfusion has been associated with reduced rate of death. Glasgow-Blatchford score is used to determine whether a person should be treated inside a hospital or as an outpatient. Intravenous PPIs can suppress stomach bleeding more quickly than oral ones. A neutral stomach pH is required to keep platelets in place and prevent clot lysis. Tranexamic acid and antifibrinolytic agents are not useful in treating peptic ulcer disease.

Peptic ulcer disease

Diet does not play an important role in either causing or preventing ulcers. Treatment includes stopping smoking, stopping use of NSAIDs, stopping alcohol, and taking medications to decrease stomach acid. The medication used to decrease acid is usually either a proton pump inhibitor (PPI) or an H2 blocker, with four weeks of treatment initially recommended. Ulcers due to H. pylori are treated with a combination of medications, such as amoxicillin, clarithromycin, and a PPI. Antibiotic resistance is increasing and thus treatment may not always be effective. Bleeding ulcers may be treated by endoscopy, with open surgery typically only used in cases in which it is not successful.

Gastrointestinal bleeding

Peptic ulcers Based on evidence from people with other health problems crystalloid and colloids are believed to be equivalent for peptic ulcer bleeding. Proton pump inhibitors (PPI) may reduce mortality in those with severe disease as well as the risk of re-bleeding and the need for surgery among this group. Oral and intravenous formulations may be equivalent; however, the evidence to support this is suboptimal. In those with less severe disease and where endoscopy is rapidly available, they are of less immediate clinical importance. There is tentative evidence of benefit for tranexamic acid which inhibits clot breakdown. Somatostatin and octreotide, while recommended for varicial bleeding, have not been found to be of general use for non variceal bleeds. After treatment of a high risk bleeding ulcer endoscopically giving a PPI once or a day rather than as an infusion appears to work just as well and is less expensive (the method may be either by mouth or intravenously).

Gastrointestinal bleeding

The benefits versus risks of placing a nasogastric tube in those with upper GI bleeding are not determined. Endoscopy within 24 hours is recommended, in addition to medical management. A number of endoscopic treatments may be used, including: epinephrine injection, band ligation, sclerotherapy, and fibrin glue depending on what is found. Prokinetic agents such as erythromycin before endoscopy can decrease the amount of blood in the stomach and thus improve the operators view. They also decrease the amount of blood transfusions required. Early endoscopy decreases hospital and the amount of blood transfusions needed. A second endoscopy within a day is routinely recommended by some but by others only in specific situations. Proton pump inhibitors, if they have not been started earlier, are recommended in those in whom high risk signs for bleeding are found. High and low dose PPIs appear equivalent at this point. It is also recommended that people with high risk signs are kept in hospital

Surgery_Schwartz

surgeonResuscitateContinuous IV PPI dripEGDLifelong acid suppressionTest + Rx H. pyloriAvoid NSAIDs/ASA if possibleYesShock?NoYesTransfusion?NoYesActive bleeding on EGD?NoYesVisible vessel on EGD?NoYesAbnormal PT, PTT, or platelets?NoFigure 26-42. Algorithm for the treatment of bleeding peptic ulcer. ASA = acetylsalicylic acid; EGD = esophagogastroduodenoscopy; O.R. = operating room; PPI = proton pump inhibitor; PRBC = unit of packed red blood cells; PT = prothrombin time; PTT = partial throm-boplastin time; Rx = treatment.Brunicardi_Ch26_p1099-p1166.indd 113401/03/19 7:12 PM 1135STOMACHCHAPTER 26Operation for bleeding peptic ulcerYesYesNoGastric ulcerDuodenal ulcerType 1,2,3Distal gastrectomy**Hemodynamically unstable?OrHigh operative risk?Csendes procPauchet procKelling-Madlener proc(see text)*Add lifelong PPI**Add TV for type 2 + 3Oversew + TV/DOversew + TV/ABMI < 21? ordifficult duodenum?Type 4RebleedRebleedDuodenal ulcer*Gastric ulcer*1) Bx and oversew2) Wedge

Surgery_Schwartz

(1st ant. tier)Duod.Cushingseromuscularsuture (2nd ant. tier)Posteriorthrough &through sutureFigure 26-38. A through D. Jaboulay pyloroplasty. ant. = anterior; Duod. = duodenum; Stom. = stomach. (Reproduced with permission from Zuidema GD: Shackelford’s Surgery of the Alimentary Tract, 4th ed. Philadelphia, PA: Elsevier/Saunders; 1996.)Brunicardi_Ch26_p1099-p1166.indd 113101/03/19 7:12 PM 1132SPECIFIC CONSIDERATIONS PART IIresuscitated and started on IV PPI.125 Most patients will stop bleeding with these measures alone, but about 25% will continue to bleed or will rebleed in hospital. It is important to identify this high-risk group early with clinical and endoscopic parameters because, essentially, all the deaths from bleeding ulcer occur in this group. Surgical consultation is mandatory, and endoscopic hemostatic therapy (cautery, epinephrine injection, clipping) is indicated and usually successful in these high-risk patients.126 Indications for operation include massive

Initial factors predicting rebleeding and death in bleeding peptic ulcer disease.

Bleeding peptic ulcer constitutes approximately half of the cases admitted with upper gastrointestinal bleeding. Although the bleeding episode stops spontaneously in most of them, rebleeding occurs in as much as 10-30% of them and has a mortality rate of 5-10%. In this study, we have evaluated the possible significant predictors associated with this adverse outcome. The records of 205 patients admitted to gastrointestinal bleeding unit (GIBU) in Riyadh Central Hospital, during the period May 1996 through to April 1999, with endoscopic confirmed diagnosis of bleeding peptic ulcer disease were reviewed for demography, clinical presentation, hematology, biochemistry, initial blood pressure, nasogastric lavage color, co-morbid disease and endoscopic findings. All the significant factors found initially (P<0.05) were entered into odds ratio and its 95% confidence interval and finally the unconditioned logistic regression model was used to find out the significant independent predictors for both rebleeding and mortality in these patients. The majority of patients (85%) were males and below the age of 60 (73%). Duodenal ulcer was the source of bleeding in 84%. Endoscopy was performed in all patients within 24 hours of admission. Only 15% were actively bleeding at the time of initial endoscopy. Thirty-six patients (17%) rebelled, majority within 72 hours of initial hemostasis. Overall, 11 patients (5%) died, 6 of them were rebleeders. Initial presentation of systolic blood pressure <100 mm Hg, blood in nasogastric tube and visible vessel within the ulcer in endoscopy were independent predictors of rebleeding while initial systolic blood pressure <100 mm Hg and age >60-years were independent predictors of mortality. Improvement of outcome in patients with bleeding peptic ulcer disease can be achieved by early detection of those patients who are at risk of adverse outcome. Patients with the above mentioned independent predictors of rebleeding and mortality are best managed in the intensive care unit with endoscopic hemostasis and proton pump inhibitor (PPI) therapy for a minimum of 5-days of admission.

Endoclip

Endoclips have found a primary application in hemostasis (or the stopping of bleeding) during endoscopy of the upper (through gastroscopy) or lower (through colonoscopy) gastrointestinal tract. Many bleeding lesions have been successfully clipped, including bleeding peptic ulcers, Mallory-Weiss tears of the esophagus, Dieulafoy's lesions, stomach tumours, and bleeding after removal of polyps. Bleeding peptic ulcers require endoscopic treatment if they show evidence of high risk stigmata of re-bleeding, such as evidence of active bleeding or oozing on endoscopy or the presence of a visible blood vessel around the ulcer. The alternatives to endoscopic clipping of peptic ulcers are thermal therapy (such as electrocautery to burn the vessel causing the bleeding), or injection of epinephrine to constrict the blood vessel. Comparative studies between endoclips and thermal therapy make the point that endoclips cause less trauma to the mucosa around the ulcer than electrocautery, but no

Surgery_Schwartz

be stopped after 3 months if the ulcerogenic stimulus (e.g., H pylori, NSAIDs, or aspirin) has been removed. However, long-term maintenance PPI therapy should be considered in all patients admitted to hospital with ulcer complications, all high-risk patients on NSAIDs or aspi-rin (the elderly or debilitated), and all patients requiring anti-coagulation or antiplatelet agents or those with a history of recurrent ulcer or bleeding. Consideration should also be given to maintenance PPI therapy in refractory smokers with a history of peptic ulcer. Sucralfate acts locally on mucosal defects and is well tolerated, and occasionally it is useful as a supplement to acid suppression.2Peptic ulcer40%24%6%4%6%5%10%5%No obvious causeOtherNeoplasmErosive diseaseMallory-Weiss syndromeOesophagitisVaricesFigure 26-31. Causes of upper GI bleeding. (Reproduced with permission from Dallal HJ, Palmer KR: ABC of the upper gastro-intestinal tract: Upper gastrointestinal haemorrhage, BMJ. 2001 Nov

Gastrointestinal bleeding

Prognosis Death in those with a GI bleed is more commonly due to other illnesses (some of which may have contributed to the bleed, such as cancer or cirrhosis) than the bleeding itself. Of those admitted to a hospital because of a GI bleed, death occurs in about 7%. Despite treatment, re-bleeding occurs in about 7–16% of those with upper GI bleeding. In those with esophageal varices, bleeding occurs in about 5–15% a year and if they have bled once, there is a higher risk of further bleeding within six weeks. Testing and treating H. pylori if found can prevent re-bleeding in those with peptic ulcers. The benefits versus risks of restarting blood thinners such as aspirin or warfarin and anti-inflammatories such as NSAIDs need to be carefully considered. If aspirin is needed for cardiovascular disease prevention, it is reasonable to restart it within seven days in combination with a PPI for those with nonvariceal upper GI bleeding.

Therapeutic endoscopy

A number of different techniques have been developed to allow treatment to be carried out endoscopically, to treat disorders such as bleeding, strictures and polyps. Types of endoscopic therapy Endoscopic haemostasis Endoscopic injection of bleeding peptic ulcers with adrenaline has been practised since the 1970s, endoscopic heater probes have been used since the 1980s, and Argon plasma coagulation has been used since the 1990s. More recently, adrenaline injection tends to be combined with either heater probe coagulation or argon plasma coagulation to minimize the chance of an ulcer rebleeding. The disadvantage of this treatment is a low risk of perforation of the gastric wall and a low risk of peritonitis. Combined therapy may work better than epinephrine alone. However, there is no evidence that one kind of treatment is more effective than the other.

Proton-pump inhibitor

Medical uses These medications are used in the treatment of many conditions, such as: Dyspepsia Peptic ulcer disease including after endoscopic treatment for bleeding As part of Helicobacter pylori eradication therapy Gastroesophageal reflux disease (GERD or GORD) including symptomatic endoscopy-negative reflux disease and associated laryngopharyngeal reflux causing laryngitis and chronic cough Barrett's esophagus Eosinophilic esophagitis Stress gastritis and ulcer prevention in critical care Gastrinomas and other conditions that cause hypersecretion of acid including Zollinger–Ellison syndrome (often 2–3x the regular dose is required)

Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). Main Recommendations MR1. ESGE recommends immediate assessment of hemodynamic status in patients who present with acute upper gastrointestinal hemorrhage (UGIH), with prompt intravascular volume replacement initially using crystalloid fluids if hemodynamic instability exists (strong recommendation, moderate quality evidence). MR2. ESGE recommends a restrictive red blood cell transfusion strategy that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target hemoglobin should be considered in patients with significant co-morbidity (e. g., ischemic cardiovascular disease) (strong recommendation, moderate quality evidence). MR3. ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Outpatients determined to be at very low risk, based upon a GBS score of 0 - 1, do not require early endoscopy nor hospital admission. Discharged patients should be informed of the risk of recurrent bleeding and be advised to maintain contact with the discharging hospital (strong recommendation, moderate quality evidence). MR4. ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence). MR5. ESGE does not recommend the routine use of nasogastric or orogastric aspiration/lavage in patients presenting with acute UGIH (strong recommendation, moderate quality evidence). MR6. ESGE recommends intravenous erythromycin (single dose, 250 mg given 30 - 120 minutes prior to upper gastrointestinal [GI] endoscopy) in patients with clinically severe or ongoing active UGIH. In selected patients, pre-endoscopic infusion of erythromycin significantly improves endoscopic visualization, reduces the need for second-look endoscopy, decreases the number of units of blood transfused, and reduces duration of hospital stay (strong recommendation, high quality evidence). MR7. Following hemodynamic resuscitation, ESGE recommends early (≤ 24 hours) upper GI endoscopy. Very early (< 12 hours) upper GI endoscopy may be considered in patients with high risk clinical features, namely: hemodynamic instability (tachycardia, hypotension) that persists despite ongoing attempts at volume resuscitation; in-hospital bloody emesis/nasogastric aspirate; or contraindication to the interruption of anticoagulation (strong recommendation, moderate quality evidence). MR8. ESGE recommends that peptic ulcers with spurting or oozing bleeding (Forrest classification Ia and Ib, respectively) or with a nonbleeding visible vessel (Forrest classification IIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or rebleeding (strong recommendation, high quality evidence). MR9. ESGE recommends that peptic ulcers with an adherent clot (Forrest classification IIb) be considered for endoscopic clot removal. Once the clot is removed, any identified underlying active bleeding (Forrest classification Ia or Ib) or nonbleeding visible vessel (Forrest classification IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality evidence). MR10. In patients with peptic ulcers having a flat pigmented spot (Forrest classification IIc) or clean base (Forrest classification III), ESGE does not recommend endoscopic hemostasis as these stigmata present a low risk of recurrent bleeding. In selected clinical settings, these patients may be discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong recommendation, moderate quality evidence). MR11. ESGE recommends that epinephrine injection therapy not be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modality (strong recommendation, high quality evidence). MR12. ESGE recommends PPI therapy for patients who receive endoscopic hemostasis and for patients with adherent clot not receiving endoscopic hemostasis. PPI therapy should be high dose and administered as an intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality evidence). MR13. ESGE does not recommend routine second-look endoscopy as part of the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). However, in patients with clinical evidence of rebleeding following successful initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with hemostasis if indicated. In the case of failure of this second attempt at hemostasis, transcatheter angiographic embolization (TAE) or surgery should be considered (strong recommendation, high quality evidence). MR14. In patients with NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence of Helicobacter pylori in the acute setting with initiation of appropriate antibiotic therapy when H. pylori is detected. Re-testing for H. pylori should be performed in those patients with a negative test in the acute setting. Documentation of successful H. pylori eradication is recommended (strong recommendation, high quality evidence). MR15. In patients receiving low dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding, ESGE recommends aspirin be resumed immediately following index endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended, provided that adequate hemostasis has been established (strong recommendation, moderate quality evidence).

[Diagnosis of gastric ulcer in the elderly].

It is well known that gastric ulcers are most often found at anglus and upper corpus in the elderly. The number of gastric ulcer found at upper corpus hold half of all cases in the elderly patients with bleeding ulcer. Sixty percent of the elderly patients with bleeding ulcer took NSAIDs including low-dose aspirin in authors' hospital. Now it is easy to treat and cure bleeding ulcers due to development of endoscopic hemostasis and antiulcer drugs such as proton pump inhibitor(PPI). However, the elderly patients sometimes result in fatal outcome on bleeding from gastric ulcer. Therefore, it is important to prevent ulcer complications by PPI for the high-risk group such as elderly patients taking NSAIDs.

Gastric Ulcer -- Treatment / Management

The goal of treatment and management of gastric ulcers is first to increase the gastric pH and allowing the gastric mucosa to heal, which is possible through administering proton pump inhibitors, such as pantoprazole. A decision to proceed with an EGD should be the next consideration. Alarm symptoms should be recognized, which would make the need for an EGD more urgent. Alarm symptoms include unintentional weight loss, bleeding, age over 50, nausea, and vomiting. If a gastric ulcer is present on EGD, biopsies of the mucosa surrounding the ulcer will b necessary to rule out gastritis, Helicobacter pylori infection, and malignancy. These patients need to be on PPI therapy twice daily for 8 weeks and then undergo a repeat endoscopy to confirm for healing. [4]

[The role of endoscopy in the hemorrhagic complications of gastroduodenal ulcer].

The hemorrhage is a fairly frequent event in the evolution of the gastroduodenal peptic ulcer syndrome. The mortality rate has remained approximately unchanged, in spite of the progress in instrumental diagnosis and medical therapy, in the last decade. The authors examine 163 cases of digestive hemorrhage from gastroduodenal ulcers, observed in the last five years (1984-1988), with particular reference to the medical or surgical treatment undertaken, and to the mortality rate. Gastroduodenal ulcers, in 340 cases of upper digestive hemorrhage, represented nearly half the lesions, registered in the same period. Duodenal ulcers (D.U.), were found in 124 patients (34.4%) and gastric ulcers (G.U.) in 39 patients (11.47%), 113 (91.1%) patients with D.U., and 33 (84.6%) patients with G.U. were treated by medical therapy. The mortality rate in this group was 6.16%. II patients (8.9%) with D.U. and 6 patients (15.3%) with G.U. were operated on. The surgical mortality rate was high at 35.2%. Total mortality rate was 9.2%. The endoscopic exam was useful for diagnostic bleeding investigation and contributed to therapeutic decisions. Active bleeding lesions were found in 38.4% of patients with G.U. and in 32.3% with D.U. In 61.6% of patients with G.U. and in 67.7% with D.U., the lesions had already stopped bleeding; but in both lesions nearly 40% of cases, presented signs of a recent hemorrhage. The prognosis and natural history of the hemorrhage, was not changed by an immediate exam. The clinical reports and the data furnished, especially from continuous bleeding and rebleeding lesions, could be useful in identifying a sub-group of patients who could obtain better results by surgical treatment within a suitable time. The endoscopy, besides selecting and contributing to a better therapeutic strategy, through haemostasis technic, could reduce mortality rate from gastroduodenal ulcer lesions.

Randomized Controlled Trial of Over-the-Scope Clip as Initial Treatment of Severe Nonvariceal Upper Gastrointestinal Bleeding.

No prior randomized controlled trial (RCT) has reported patient outcomes of large over-the-scope clip (OTSC) compared to standard hemostasis as initial endoscopic treatment of severe NVUGIB. This was our study aim. Patients with bleeding ulcers or Dieulafoy's lesions and major stigmata of hemorrhage - SRH (active spurting bleeding, visible vessel, or clot) - or lesser SRH (oozing bleeding or flat spots - with arterial blood flow by Doppler probe) were randomized to OTSC or standard endoscopic hemostasis (with hemoclips or multipolar electrocoagulation - MPEC). Patients and their healthcare providers were blinded to treatments and made all post-randomization management decisions. Ulcer patients received high dose intravenous infusions of proton pump inhibitors (PPI) for 3 days, then 27 days of oral PPI. 30 day outcomes were prospectively recorded; data management was with SAS; and data analysis was by a statistician. 53 patients (25 OTSC, 28 Standard) were randomized, with similar baseline risk factors. However, there were significant differences in OTSC vs. Standard groups in rates of rebleeding (4% vs. 28.6%; p = .017; relative risk 0.10, 95% confidence intervals 0.01, 0.91; number needed to treat 4); severe complications (0 % vs. 14.3%); and post-randomization units of red cell transfusions (0.04 vs. 0.68). All rebleeds occurred in patients with major SRH and none with lesser SRH. 1. OTSC significantly reduced rates of rebleeding, severe complications, and post-randomization red cell transfusions. 2. Patients with major stigmata benefited significantly from hemostasis with OTSC, but those with lesser stigmata did not. (ClinicalTrials.gov, Number: NCT03065465).

Marginal zone B-cell lymphoma

Primary rectal EMZL, more commonly termed MALT lymphoma of the rectum, usually presents at an early stage of disease with anal bleeding and/or blood in the stool. Endoscopic examination reveals a rectal polyp, rectal mass, or, less commonly, a rectal ulcer. Some cases of this lymphoma have been reported to regress spontaneously. On examination, >90% of cases present with localized (i.e. stage I or II) disease. The lymphomas' lesions are characterized by reactive lymphoid follicles infiltrated with centrocyte-like or monocyte-like B cells (the latter cells may show features of plasma cells). The malignant cells in these lesions may contain the t(11;18) translocation and therefore express the API2-MALT1 chimeric protein (11% of cases). Some 22-45% of casests are associated with Helicobactor pylori GI tract infection. Treatments for the disease have included radiotherapy, surgical resection, endoscopic mucosal resection, various chemotherapies, and antibiotic-based eradication of

[Treatment of gastroduodenal ulcer bleedings in a general hospital of emergency care].

Treatment of patients with gastroduodenal ulcer bleedings in a general hospital of emergency care is a complex of measures including of endoscopic diagnosis and stopping of bleeding, use of effective antisecretory drugs with obligatory laboratory control of acid-producing function of the stomach, surgical treatment and eradication of H. pylori. Up-to-date methods of endoscopic hemostasis - spirituous infiltration, argon-plasma coagulation, clipping of vessels in ulcer and also their combination in difficult cases - provide reliable hemostasis and allow to avoid urgent surgery. Recently we succeeded in reducing the rate of urgent surgeries performed at the height of bleedings from 70 to 40%. These methods can be recommended for clinical practice because they reduce significantly lethality rates in patients with severe conditions.

Management of patients with ulcer bleeding.

This guideline presents recommendations for the step-wise management of patients with overt upper gastrointestinal bleeding. Hemodynamic status is first assessed, and resuscitation initiated as needed. Patients are risk-stratified based on features such as hemodynamic status, comorbidities, age, and laboratory tests. Pre-endoscopic erythromycin is considered to increase diagnostic yield at first endoscopy. Pre-endoscopic proton pump inhibitor (PPI) may be considered to decrease the need for endoscopic therapy but does not improve clinical outcomes. Upper endoscopy is generally performed within 24h. The endoscopic features of ulcers direct further management. Patients with active bleeding or non-bleeding visible vessels receive endoscopic therapy (e.g., bipolar electrocoagulation, heater probe, sclerosant, clips) and those with an adherent clot may receive endoscopic therapy; these patients then receive intravenous PPI with a bolus followed by continuous infusion. Patients with flat spots or clean-based ulcers do not require endoscopic therapy or intensive PPI therapy. Recurrent bleeding after endoscopic therapy is treated with a second endoscopic treatment; if bleeding persists or recurs, treatment with surgery or interventional radiology is undertaken. Prevention of recurrent bleeding is based on the etiology of the bleeding ulcer. H. pylori is eradicated and after cure is documented anti-ulcer therapy is generally not given. Nonsteroidal anti-inflammatory drugs (NSAIDs) are stopped; if they must be resumed low-dose COX-2-selective NSAID plus PPI is used. Patients with established cardiovascular disease who require aspirin should start PPI and generally re-institute aspirin soon after bleeding ceases (within 7 days and ideally 1-3 days). Patients with idiopathic ulcers receive long-term anti-ulcer therapy.

A case of hypereosinophilic syndrome presenting with intractable gastric ulcers.

We report a rare case of hypereosinophilic syndrome (HES) presenting with intractable gastric ulcers. A 71-year-old man was admitted with epigastric pain. Initial endoscopic findings revealed multiple, active gastric ulcers in the gastric antrum. He underwent Helicobacter pylori (H pylori) eradication therapy followed by proton pump inhibitor (PPI) therapy. However, follow-up endoscopy at 4, 6, 10 and 14 mo revealed persistent multiple gastric ulcers without significant improvement. The proportion of his eosinophil count increased to 43% (total count: 7903/mm(3)). Abdominal-pelvic and chest computed tomography scans showed multiple small nodules in the liver and both lungs. The endoscopic biopsy specimen taken from the gastric antrum revealed prominent eosinophilic infiltration, and the liver biopsy specimen also showed eosinophilic infiltration in the portal tract and sinusoid. A bone marrow biopsy disclosed eosinophilic hyperplasia as well as increased cellularity of 70%. The patient was finally diagnosed with HES involving the stomach, liver, lung, and bone marrow. When gastric ulcers do not improve despite H pylori eradication and prolonged PPI therapy, infiltrative gastric disorders such as HES should be considered.

Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

To evaluate the clinical effectiveness and cost-effectiveness of proton pump inhibitors (PPIs) in the prevention and treatment of acute upper gastrointestinal (UGI) haemorrhage, as well as to compare this with H2-receptor antagonist (H2RA), Helicobacter pylori eradication (in infected patients) or no therapy, for the prevention of first and/or subsequent bleeds among patients who continue to use non-steroidal anti-inflammatory drugs (NSAIDs). Also to evaluate the clinical effectiveness of PPI therapy, compared with other treatments, for the prevention of subsequent bleeds in patients who had previously experienced peptic ulcer (PU) bleeding. Electronic databases and major conference proceedings were searched up to February 2006. Data were collected from the systematic reviews addressing each research objective. These were then entered into an economic model to compare the costs and quality-adjusted life-days of alternative management strategies over a 28-day period for patients who have had UGI bleeding. A Markov model with a Monte Carlo simulation used data from the systematic reviews to identify the most cost-effective treatment strategy for the prevention of UGI bleeding (first and subsequent) among NSAID users using an outcome of costs per quality-adjusted life-years (QALYs) over a lifetime from age 50 years. PPI treatment initiated after endoscopic diagnosis of PU bleeding significantly reduced re-bleeding and surgery compared with placebo or H2RA. Although there was no evidence of an overall effect of PPI treatment on all-cause mortality, PPIs significantly reduced mortality in subgroups when studies conducted in Asia were examined in isolation or when the analysis was confined to patients with high-risk endoscopic findings. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduced the proportion of patients with stigmata of recent haemorrhage (SRH) at index endoscopy compared with placebo or H2RA, but there was no evidence that PPI treatment affected clinically important outcomes. Giving oral PPI both before and after endoscopy, with endoscopic haemostatic therapy (EHT) for those with major SRH, is preferred to all others on cost-effectiveness grounds at any threshold over 25,000 pounds per QALY, even if only short-term effects are taken into account, and at any threshold over 200 pounds per life-year gained if long-term effects are included. The risk of NSAID-induced endoscopic gastric and duodenal ulcers was reduced by standard doses of PPI and misoprostol, and double doses of H2RAs. Standard doses of H2RAs reduced the risk of endoscopic duodenal ulcers. PPIs reduced NSAID-induced dyspepsia. PPIs were superior to misoprostol in preventing recurrence of NSAID-induced endoscopic duodenal ulcers, but PPIs were comparable to misoprostol in preventing the recurrence of NSAID-induced endoscopic gastric ulcers. Full-dose misoprostol reduced bleeding, perforation or gastric outlet obstruction due to NSAID-induced ulcers, but misoprostol was poorly tolerated and associated with frequent adverse effects. H. pylori eradication treatment was equally effective with PPI treatment for the primary or secondary prevention of endoscopic ulcers in NSAID users. H. pylori eradication treatment was more effective than placebo for the primary prevention of endoscopic PU and for the prevention of re-bleeding from PU in NSAID users. With regard to primary and secondary prevention of bleeding PU in NSAID users, the two most cost-effective strategies are H. pylori eradication alone, and H. pylori eradication followed by misoprostol (substituted by a PPI, if misoprostol is not tolerated) at an additional 4810 pounds per QALY. In patients who had previously experienced a bleed from a PU, re-bleeding was less frequent after H. pylori eradication therapy than after non-eradication antisecretory therapy, whether or not the latter was combined with long-term maintenance antisecretory therapy. PPI treatment compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduces the proportion of patients with SRH at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with EHT for those with major SRH, is likely to be the most cost-effective. Treatment of H. pylori infection was found to be more effective than antisecretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone or eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies for preventing bleeding ulcers among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective. Further large randomised controlled trials are needed to address areas such as PPI administration prior to endoscopic diagnosis, different doses and administration of PPIs, as well as the primary and secondary prevention of UGI bleeding.


This is a case of hyperchloremic metabolic acidosis with normal anion gap. Severe metabolic acidosis causes myocardial contractile depression, reduced effectiveness of catecholamines, increased incidence of arrhythmias, vasodilatation and increased capillary permeability, with the consequent reduction of tissue flow, at the cerebral level (leading to states of confusion and even coma), at the renal level, at the hepatic level... These patients frequently present intense tachypnea (Kussmaul's breathing) in an attempt to compensate for MCA by hyperventilation. We must take into account that, in this case, potassium is decreased, so the most frequent cause (supported by the stains on the dress) would be diarrhea, so it is most likely that their renal failure (although they do not give us urine ion data to confirm it) is of prerenal type. The treatment would be water and electrolyte replacement and, in principle, unless the patient worsens and the pH is less than 7.10, we should not administer bicarbonate.

This is a case of hyperchloremic metabolic acidosis with normal anion gap. Severe metabolic acidosis causes myocardial contractile depression, reduced effectiveness of catecholamines, increased incidence of arrhythmias, vasodilatation and increased capillary permeability, with the consequent reduction of tissue flow, at the cerebral level (leading to states of confusion and even coma), at the renal level, at the hepatic level... These patients frequently present intense tachypnea (Kussmaul's breathing) in an attempt to compensate for MCA by hyperventilation. We must take into account that, in this case, potassium is decreased, so [HIDDEN], so it is most likely that their renal failure (although they do not give us urine ion data to confirm it) is of prerenal type. The treatment would be water and electrolyte replacement and, in principle, unless the patient worsens and the pH is less than 7.10, we should not administer bicarbonate.

Elderly woman brought to the ER by her neighbors because they see her somewhat groggy and with stool stains on her clothes. BP 100/60 mmHg, HR 100 bpm, sitting 70/30, HR 105 bpm. PVY normal. Kussmaul's respiration. No neurological focality. Weight 50 kg. Lab: PH 7.25, PCO2 14, Bicarbonate 5, Na 133, K 2.5, Cl 118, Creat 3.4, NUS 60, Prot 8. Which of the following answers is correct?

The presenting acid-base disorder is a respiratory acidosis.

Compensation to correct the acidosis is inadequate.

With this exploration, we rule out that she is dehydrated.

In any case, we should not put bicarbonate.

She has an acute renal failure of prerenal cause.

ANESTHESIOLOGY, CRITICAL CARE AND EMERGENCY MEDICINE

Base excess

Interpretation Base excess beyond the reference range indicates metabolic alkalosis if too high (more than +2 mEq/L) metabolic acidosis if too low (less than −2 mEq/L) Blood pH is determined by both a metabolic component, measured by base excess, and a respiratory component, measured by PaCO2 (partial pressure of carbon dioxide). Often a disturbance in one triggers a partial compensation in the other. A secondary (compensatory) process can be readily identified because it opposes the observed deviation in blood pH. For example, inadequate ventilation, a respiratory problem, causes a buildup of CO2, hence respiratory acidosis; the kidneys then attempt to compensate for the low pH by raising blood bicarbonate. The kidneys only partially compensate, so the patient may still have a low blood pH, i.e. acidosis. In summary, the kidneys partially compensate for respiratory acidosis by raising blood bicarbonate.

Simple acid-base disorders.

The body regulates pH closely to maintain homeostasis. The pH of blood can be represented by the Henderson-Hasselbalch equation: pH = pK + log [HCO3-]/PCO2 Thus, pH is a function of the ratio between bicarbonate ion concentration [HCO3-] and carbon dioxide tension (PCO2). There are four simple acid base disorders: (1) Metabolic acidosis, (2) respiratory acidosis, (3) metabolic alkalosis, and (4) respiratory alkalosis. Metabolic acidosis is the most common disorder encountered in clinical practice. The respiratory contribution to a change in pH can be determined by measuring PCO2 and the metabolic component by measuring the base excess. Unless it is desirable to know the oxygenation status of a patient, venous blood samples will usually be sufficient. Metabolic acidosis can result from an increase of acid in the body or by excess loss of bicarbonate. Measurement of the "anion-gap" [(Na+ + K+) - (Cl- + HCO3-)], may help to diagnose the cause of the metabolic acidosis. Treatment of all acid-base disorders must be aimed at diagnosis and correction of the underlying disease process. Specific treatment may be required when changes in pH are severe (pH less than 7.2 or pH greater than 7.6). Treatment of severe metabolic acidosis requires the use of sodium bicarbonate, but blood pH and gases should be monitored closely to avoid an "overshoot" alkalosis. Changes in pH may be accompanied by alterations in plasma potassium concentrations, and it is recommended that plasma potassium be monitored closely during treatment of acid-base disturbances.

Metabolic acidosis

Diagnostic approach and causes Metabolic Acidosis is defined as a reduced serum pH, and an abnormal serum bicarbonate concentration of <22 mEq/L, below the normal range of 22 to 29 mEq/L. However, if a patient has other coexisting acid-base disorders, the pH level may be low, normal or high in the setting of metabolic acidosis. In the absence of chronic respiratory alkalosis, metabolic acidosis can be clinically diagnosed by measuring serum bicarbonate levels in the blood, which is generally a standard component of blood panels. Imperatively, when weighing a metabolic acidosis diagnosis, the change in serum bicarbonate levels over time should be considered; if baseline bicarbonate results are unknown, a single set of values may be misinterpreted. Causes Generally, metabolic acidosis occurs when the body produces too much acid (e.g., lactic acidosis, see below section), there is a loss of bicarbonate from the blood, or when the kidneys are not removing enough acid from the body.

Respiratory acidosis

Types Respiratory acidosis can be acute or chronic. In acute respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference range (over 6.3 kPa or 45 mm Hg) with an accompanying acidemia (pH <7.36). In chronic respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference range, with a normal blood pH (7.35 to 7.45) or near-normal pH secondary to renal compensation and an elevated serum bicarbonate (HCO3− >30 mEq/L). Causes Acute Acute respiratory acidosis occurs when an abrupt failure of ventilation occurs. This failure in ventilation may be caused by depression of the central respiratory center by cerebral disease or drugs, inability to ventilate adequately due to neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis, Guillain–Barré syndrome, muscular dystrophy), or airway obstruction related to asthma or chronic obstructive pulmonary disease (COPD) exacerbation.

Physiology_Levy

Table 37.2 ). In an appropriately compensated metabolic acidosis, the PCO2 is decreased, whereas it is elevated in compensated metabolic alkalosis. With respiratory acidosis, compensation results in an elevation of the [HCO3 −]. Conversely, ECF [HCO3 −] is reduced in response to respiratory alkalosis. In this example, the PCO2 is reduced from normal, and the magnitude of this reduction (10 mm Hg decrease in PCO2 for an 8 mEq/L decrease in ECF [HCO3 −]) is as expected (see Table 37.2 ). Therefore the acid-base disorder is a simple metabolic acidosis with appropriate respiratory compensation. A mixed acid-base disorder reflects the presence of two or more underlying causes for the acid-base disturbance. For example, consider the following data: pH = .6 96

Metabolic alkalosis

To calculate the expected pCO2 in the setting of metabolic alkalosis, the following equations are used: pCO2 = 0.7 [HCO3] + 20 mmHg ± 5 pCO2 = 0.7 [HCO3] + 21 mmHg Treatment To effectively treat metabolic alkalosis, the underlying cause(s) must be corrected. A trial of intravenous chloride-rich fluid is warranted if there is a high index of suspicion for chloride-responsive metabolic alkalosis caused by loss of gastrointestinal fluid (e.g., due to vomiting). Terminology Alkalosis refers to a process by which the pH is increased. Alkalemia refers to a pH which is higher than normal, specifically in the blood. See also Hypokalemia Metabolic acidosis Respiratory acidosis Respiratory alkalosis References External links Acid–base disturbances

Acute acid-base disorders. 2. Specific disturbances.

Evaluation of the acid-base status of the body requires measurement of bicarbonate (total carbon dioxide) concentration, pH, and partial pressure of CO2 in arterial blood. Calculation of standard bicarbonate and base excess or deficit is not necessary. The normal concentration of free hydrogen ions (H+) is approximately 40 millimoles/liter, which is equivalent to a pH of 7.4. The normal load of fixed acids is 50 to 80 millimoles in 24 hours. A steady state is maintained by excretion of an equal amount of H+ by the kidneys, which at the same time regenerate bicarbonate to replenish buffer stores. Renal excretion of H+ is in the form of titratable acid and ammonium. Synthesis of ammonia can increase severalfold under the stimulus of acidosis. This is the chief mechanism of long-term compensation. Metabolic acidosis can be due to an excessive acid load (endogenous or exogenous), impaired renal excretion of H+, or bicarbonate loss. Determination of the "anion gap" (unmeasured anions) helps to establish the mechanism of acidosis. Acidosis with a normal anion gap is due to either bicarbonate loss or ingestion of certain chloride salts. A gap larger than normal indicates the presence in the body of acids other than acidfying chloride salts. Management of metabolic acidosis requires accurate diagnosis, clear understanding of the mechansim, and individualized treatment. Metabloic alkalosis is due to loss of H+ (usually from stomach or kidneys) or ingestion of alkali. Measurement of urinary chloride helps establish the mechanism of alkalosis. In saline-responsive alkalosis, the urinary chloride level is very low. This is usually due to gastric loss of H+, and the condition responds to administration of saline solution. When the urinary chloride level is only moderately low, the alkalosis is probably not due to gastric loss of H+. This form of alkalosis (saline-resistant) does not respond well to administration of saline solution and requires use of potassium in treatment. Apprpriate compensatory responses to acidosis or alkalosis are critical to survival. Compensation for metabloic acidosis consists of hyperventilation and enhanced renal excretion of H+, chiefly as ammonium. In metabolic alkalosis, compensation is mainly renal excretion of bicarbonate. Respiratory acidosis is due to alveolar hypoventilation. In chronic situations, a compensatory rise in serum bicarbonate concentration is expected. Management consists of treatment of the cause of hypoventilation. Respiratory alkalosis is due to hyperventilation. Treatment requires identification and correction of the cause of hyperventilation.

Respiratory acidosis

Diagnosis Diagnoses can be done by doing an ABG (Arterial Blood Gas) laboratory study, with a pH <7.35 and a PaCO2 >45 mmHg in an acute setting. Patients with COPD and other Chronic respiratory diseases will sometimes display higher numbers of PaCO2 with HCO3- >30 and normal pH. Terminology Acidosis refers to disorders that lower cell/tissue pH to < 7.35. Acidemia refers to an arterial pH < 7.36. See also Acidosis Alkalosis Arterial blood gas Chemical equilibrium pCO2 pH pKa Metabolic acidosis Metabolic alkalosis Respiratory alkalosis References External links Acid–base disturbances

Base excess

A high base excess, thus metabolic alkalosis, usually involves an excess of bicarbonate. It can be caused by Compensation for primary respiratory acidosis Excessive loss of HCl in gastric acid by vomiting Renal overproduction of bicarbonate, in either contraction alkalosis or Cushing's disease A base deficit (a below-normal base excess), thus metabolic acidosis, usually involves either excretion of bicarbonate or neutralization of bicarbonate by excess organic acids. Common causes include Compensation for primary respiratory alkalosis Diabetic ketoacidosis, in which high levels of acidic ketone bodies are produced Lactic acidosis, due to anaerobic metabolism during heavy exercise or hypoxia Chronic kidney failure, preventing excretion of acid and resorption and production of bicarbonate Diarrhea, in which large amounts of bicarbonate are excreted Ingestion of poisons such as methanol, ethylene glycol, or excessive aspirin

Respiratory acidosis

In acute respiratory acidosis, compensation occurs in 2 steps. The initial response is cellular buffering (plasma protein buffers) that occurs over minutes to hours. Cellular buffering elevates plasma bicarbonate (HCO3−) only slightly, approximately 1 mEq/L for each 10-mm Hg increase in PaCO2. The second step is renal compensation that occurs over 3–5 days. With renal compensation, renal excretion of carbonic acid is increased and bicarbonate reabsorption is increased. For instance, PEPCK is upregulated in renal proximal tubule brush border cells, in order to secrete more NH3 and thus to produce more HCO3−. Estimated changes In renal compensation, plasma bicarbonate rises 3.5 mEq/L for each increase of 10 mm Hg in PaCO2. The expected change in serum bicarbonate concentration in respiratory acidosis can be estimated as follows:

Physiology_Levy

The acid-base disorder represented by these values or any other set of values can be determined using the following three-step approach: 1. Examination of the pH. When pH is considered first, the underlying disorder can be classified as either an acidosis or an alkalosis. The defense mechanisms of the body cannot correct an acid-base disorder by themselves. Thus even if the defense mechanisms are completely operative, the change in pH indicates the acid-base disorder. In the example provided, the pH of 7.35 indicates acidosis. 2. Determination of metabolic versus respiratory disorder. Simple acid-base disorders are either metabolic or

Physiology_Levy

Table 37.1 summarizes the primary alterations and the subsequent compensatory or defense mechanisms of the various simple acid-base disorders. In all acid-base disorders the compensatory response does not correct the underlying disorder but simply reduces the magnitude of the change in pH. Correction of the acid-base disorder requires treatment of its cause. Types of Acid-Base Disorders Metabolic acidosis is characterized by a decreased ECF [HCO3 −] and pH. It can develop via the addition of nonvolatile acid to the body (e.g., diabetic ketoacidosis), the loss of nonvolatile base (e.g., HCO3 − loss caused by diarrhea), or failure of the kidneys to excrete titratable acid and NH4 + (e.g., renal failure). As previously described, the buffering of H+ occurs in both the ECF and ICF compartments. When the pH falls, the respiratory centers are stimulated and the ventilatory rate is increased (respiratory compensation).

Acidosis

Acid consumption from poisoning such as methanol ingestion, elevated levels of iron in the blood, and chronically decreased production of bicarbonate may also produce metabolic acidosis. Metabolic acidosis is compensated for in the lungs, as increased exhalation of carbon dioxide promptly shifts the buffering equation to reduce metabolic acid. This is a result of stimulation to chemoreceptors, which increases alveolar ventilation, leading to respiratory compensation, otherwise known as Kussmaul breathing (a specific type of hyperventilation). Should this situation persist, the patient is at risk for exhaustion leading to respiratory failure. Mutations to the V-ATPase 'a4' or 'B1' isoforms result in distal renal tubular acidosis, a condition that leads to metabolic acidosis, in some cases with sensorineural deafness.

Renal compensation

Renal compensation is a mechanism by which the kidneys can regulate the plasma pH. It is slower than respiratory compensation, but has a greater ability to restore normal values. In respiratory acidosis, the kidney produces and excretes ammonium (NH4+) and monophosphate, generating bicarbonate in the process while clearing acid. In respiratory alkalosis, less bicarbonate (HCO3−) is reabsorbed, thus lowering the pH. References Acid–base disturbances

Winters' formula

Winters' formula, named for Dr. R.W. Winters, is a formula used to evaluate respiratory compensation when analyzing acid–base disorders and a metabolic acidosis is present. It can be given as , where HCO3− is given in units of mEq/L and pCO2 will be in units of mmHg. Winters' formula gives an expected value for the patient's PCO2; the patient's actual (measured) PCO2 is then compared to this: If the two values correspond, respiratory compensation is considered to be adequate. If the measured PCO2 is higher than the calculated value, there is also a secondary respiratory acidosis or mixed acid base disorder. If the measured PCO2 is lower than the calculated value, there is also a secondary respiratory alkalosis or mixed acid base disorder. References Respiratory therapy Mathematics in medicine

InternalMed_Harrison

Mixed acid-base disorders—defined as independently coexisting disorders, not merely compensatory responses—are often seen in patients in critical care units and can lead to dangerous extremes of pH (Table 66-2). A patient with diabetic ketoacidosis (metabolic acidosis) may develop an independent respiratory problem (e.g., limits (range of values) of the normal respiratory and metabolic compensations for primary acid-base disturbances. (From TD DuBose Jr: Acid-base disorders, in Brenner and Rector’s The Kidney, 8th ed, BM Brenner [ed]. Philadelphia, Saunders, 2008, pp 505–546, with permission.) Key: Highor normal-AG metabolic acidosis; prevailing Paco2 below predicted value (Table 66-1) Example: Na+, 140; K+, 4.0; Cl-, 106; HCO3 -, 14; AG, 20; Paco2, 24; pH, 7.39 (lactic acidosis, sepsis in ICU) Metabolic acidosis—respiratory acidosis

Arterial Blood Gas -- Results, Reporting, and Critical Findings

Example 1 [28] : ABG: pH = 7.39, PaCO 2 = 51 mm Hg, PaO 2 = 59 mm Hg, HCO 3 = 30 mEq/L and SaO 2 = 90%, on room air. pH is in the normal range, so use 7.40 as a cutoff point, in which case it is < 7.40, and acidosis is present. The elevated PaCO 2 indicates respiratory acidosis, and the elevated HCO 3 indicates a metabolic alkalosis. The value consistent with the pH is PaCO 2 . Therefore, this is a primary respiratory acidosis. The acid-base that is inconsistent with the pH is the elevated HCO3, indicating a metabolic alkalosis, so there is compensation signifying a non-acute primary disorder because it takes days for metabolic compensation to be effective. Last, the decreased PaO 2 indicates an abnormality with oxygenation. However, a history and physical will help delineate the severity and urgency of required interventions, if any. Example 2 [28] : ABG: pH = 7.45, PaCO 2 = 32 mm Hg, PaO 2 = 138 mm Hg, HCO 3 = 23 mEq/L, the base deficit = 1 mEq/L, and SaO 2 is 92%, on room air.

InternalMed_Harrison

4. Correct the metabolic acidosis. The plasma bicarbonate concentration will usually not increase for several hours because of dilution from administered IV NaCl. The plasma [HCO−] approaches 18 meq/L once ketoacidosis disappears. Sodium bicarbonate therapy is often not recommended or necessary and is contraindicated CHAPTER 64e Fluid and Electrolyte Imbalances and Acid-Base Disturbances: Case Examples 64e-2 for children. Bicarbonate is administered to adults with DKA for extreme acidemia (pH <7.1); for elderly patients (>70 years old), a threshold pH of 7.20 is recommended. Sodium bicarbonate, if administered, should only be given in small amounts. Because ketoacids are metabolized in response to insulin therapy, bicarbonate will be added to the ECF as ketoacids are converted. Overshoot alkalosis may occur from the combination of exogenously administered sodium bicarbonate plus metabolic production of bicarbonate. 5.

[Severe accidental hypothermia in an elderly woman].

Profound hypothermia (core temperature of less than 28 degrees C) is a life threatening state and a medical emergency associated with a high mortality rate. The prognosis depends on underlying diseases, advanced or very early age, the duration prior to treatment, the degree of hemodynamic deterioration, and especially, the methods of treatment, including active external or internal rewarming. This is a case study of an 80-year-old female patient with severe accidental hypothermia (core temperature 27 degrees C). She was found in her home lying immobile on the cold floor after a fall. The patient was in a profound coma with cardiocirculatory collapse, and the medical staff treating her was inclined to pronounce her deceased. On her arrival at the hospital, she was resuscitated, put on a respirator and actively warmed. Very severe metabolic disorders were found, including a marked metabolic acidosis composed of diabetic ketoacidosis (she had suffered from insulin treated type 2 diabetes mellitus) and lactic acidosis with a very high anion gap (42) and a hyperosmotic state (blood glucose 1202 mg/dl). There were pathognomonic electrocardiographic abnormalities, J-wave of Osborn and prolonged repolarization. Slow atrial fibrillation with a ventricular response of 30 bpm followed by a nodal rhythm of 12 bpm and reversible cardiac arrest were recorded. The pulse and blood pressure were unobtainable. Despite the successful resuscitation and hemodynamic and cognitive improvement, rhabdomyolysis (CKP 6580 u/L), renal failure and hepatic damage developed. She was extubated and treated with intravenous fluids containing dopamine, bicarbonate, insulin and antibiotics. Her medical condition gradually improved, and she was discharged clear minded, functioning very well and independent. Renal and liver tests returned eventually to normal limits. Progressive bradycardia, hypotension and death due to ventricular fibrillation or asystole commonly occur during severe hypothermia. Respiratory and metabolic, sometimes lactic, acidosis, lethargy and coma, hypercoagulopathy, hyperosmolar state, acute pancreatitis and renal and hepatic failure are frequent complications of hypothermia. Underlying predisposing causes of hypothermia are diabetic ketoacidosis, cerebrovascular disease, mental retardation, hypothyroidism, pituitary and adrenal insufficiency, malnutrition, acute alcoholism, liver damage, hypoglycemia, sepsis, hypothalamic dysfunction, sepsis and polypharmacy, and especially, the use of sedative and narcotic drugs. Our case demonstrates once again that CPR once begun should continue until the successful rewarming because "no one is dead until warm and dead".

[Contribution to acid-base metabolism in hypertonic dehydration by the study of "fraction R" (underterminate anions) (author's transl)].

A study on the value of "R fraction" of plasma electrolites (undetermined anions), in order to know better the metabolic acidosis of the hypertonic dehydration is achieved. "R fraction" value was obtained by the formulae: R fraction = plasma N+ --(plasma Cl- + plasma HCO3-). The mean values in patients with hypertonic dehydration was: 12.4 +/- 8.3 mEq./l., more than the normal standard data of our laboratory: 8.55 +/- 3.4 mEq./l. Authors make two groups in accordance with the "R" value: one with low "R fraction" (25 cases): 4.79 +/- 4.70 mEq./l.; and another with high "R fraction" (32 cases): 20.04 +/- 6.6 mEq./l., and compare the differences (ethiologic, clinic, shock and metabolic) between the two groups. It is confirmed that acidosis in hypertonic dehydration is essentially hyperchloremic. It was speculated on the "anion gap" and the total value of chloride in this dehydration.

InternalMed_Harrison

Metabolic acidosis can occur because of an increase in endogenous acid production (such as lactate and ketoacids), loss of bicarbonate (as in diarrhea), or accumulation of endogenous acids (as in renal failure). Metabolic acidosis has profound effects on the respiratory, cardiac, and nervous systems. The fall in blood pH is accompanied by a char acteristic increase in ventilation, especially the tidal volume (Kussmaul respiration). Intrinsic cardiac contractility may be depressed, but ino tropic function can be normal because of catecholamine release. Both present; the decrease in central and pulmonary vascular compliance predisposes to pulmonary edema with even minimal volume overload. CNS function is depressed, with headache, lethargy, stupor, and, in some cases, even coma. Glucose intolerance may also occur. There are two major categories of clinical metabolic acidosis: high-AG and non-AG, or hyperchloremic, acidosis (Table 66-3 and Table 66-4).

Delta ratio

Result 4: if the result of the ratio is greater than 2 in a high anion gap metabolic acidosis, it is usually because there was a pre-existing higher than normal bicarbonate level. This is commonly found in people with chronic respiratory acidosis from chronic lung disease such as chronic obstructive pulmonary disease (COPD), who can't breathe off their excess carbon dioxide owing to poor lung function, and retain bicarb in order to counteract the acidosis caused by the retained CO2. Alternatively it could be caused by a concurrent metabolic alkalosis such as vomiting causing acid loss and hence alkalosis, or diuretic use with loss of Cl¯ and a compensatory bicarb retention in order to maintain plasma electrical neutrality.

[Acute encephalopathy due to thiamine deficiency with hyperammonemia in a chronic hemodialysis patient: a case report].

Hemodialysis(HD) patients are at risk for thiamine deficiency because of low intake and accelerated loss of thiamine during HD. We report here an HD patient, an 82-year-old woman, who developed acute encephalopathy due to thiamine deficiency with hyperammonemia. She was admitted to Nishikawa Town Hospital due to pneumonia and was treated with ABPC/SBT for one week. While she was cured of pneumonia, she had a persistently poor appetite. On the twenty-fourth day after admission, HD with intradialytic parenteral nutrition(IDPN), which consisted of 10% glucose 500 ml, in order to correct her malnutrition, was started. She suddenly presented confusion, speech disturbance and ophthalmoplegia. HD with IDPN was stopped after two hours because of her symptoms. Laboratory studies disclosed plasma glucose of 186 mg/dl and serum ammonium of 155 micrograms/dl. Arterial blood gas analysis(inhaling 3 l/min O2) showed severe metabolic acidosis and respiratory acidosis (pH 7.138, pCO2 44.8 mmHg, pO2 108.9 mmHg, HCO3- 15.1 mmol/l). Her malnutrition, unexplained metabolic acidosis and neurological presentation raised the suspicion of acute encephalopathy due to thiamine deficiency. Fursultiamine 100 mg was administered intravenously. After two hours, metabolic acidosis disappeared (pH 7.437, pCO2 33.9 mmHg, pO2 161.0 mmHg, HCO3- 22.9 mmol/l), and she regained her clear consciousness and serum ammonium decreased at 16 micrograms/dl on the next morning. Serum lactate and thiamine level were shown later to be 57.5 mg/dl and 27 nmol/l, respectively. Her clinical course suggests that the glucose load including IDPN may have caused deterioration of the neurological disorder under the condition of thiamine deficiency. Furthermore, it is possible that a relationship exists between thiamine deficiency and hyperammonemia.

[Problems of acid-base equilibrium of the organism].

The physiopathology, clinical aspects and diagnosis of changes in Acid-Base balance are reviewed. Balance depends on diet, metabolism and efficiency of the emunctory organs (intestinal, renal and respiratory). Changes in Acid-Base balance are more frequent than is commonly thought and are also seen in out-patients whose general condition is not serious. Specific diagnosis is based exclusively on blood measurement of pH, PCO2 and HCO3. It is necessary and sufficient for the physician to remember to carry out these studies more often. It is thus possible to identify and correct initial situations of altered A-B balance which, if ignored, may aggravate general condition to a sometimes fatal extent.

Metabolic acidosis

Buffer The decreased bicarbonate that distinguishes metabolic acidosis is therefore due to two separate processes: the buffer (from water and carbon dioxide) and additional renal generation. The buffer reactions are: H+ + HCO3- <=> H2CO3 <=> CO2 + H2O The Henderson-Hasselbalch equation mathematically describes the relationship between blood pH and the components of the bicarbonate buffering system: Using Henry's law, we can say that [] = 0.03 × Pa (Pa is the pressure of in arterial blood) Adding the other normal values, we get Consequences Acute Metabolic Acidosis Acute Metabolic Acidosis most often occurs during hospitalizations, and acute critical illnesses. It is often associated with poor prognosis, with a mortality rate as high as 57% if the pH remains untreated at 7.20. At lower pH levels, acute metabolic acidosis can lead to impaired circulation and end organ function.

[Dwarfism, arterial hypertension and hyperkalemic acidosis corrected with thiazides. A case of type II pseudohypoaldosteronism].

Type II pseudohypoaldosteronism is a rare tubulopathy defined by abnormal renal potassium excretion. A 12 1/2 year-old girl, was admitted for dwarfism. Her parents were not consanguineous and her 5 living sibs were normal. At admission, she had moderate hypertension: systolic 130-150 mmHg; diastolic 80-100 mmHg and no pubertal development. pH (arterial): 7.34; bicarbonates: 18-20 mEq/l; chloride: 112-120 mEq/l; potassium: 5.6-7 mEq/l; aldosterone: 200-700 pg/ml (N < 60); plasma renin activity: 0.4 ng/ml/hr (N 2.2 +/- 0.2). The bone maturation was 8 1/2 years. All the other renal function tests were normal. The titratable acidity was 22 mEq/day (N 20-40) and the ammonia excretion 15.2 mEq/l (N 44-61). The fractional excretion of potassium was 6.5% (N 11.8 +/- 1.9). This girl was given polystyrene sulfonate resin followed by hydrochlorothiazide (1 to 3 mg/kg/day). There was a subsequent improvement in all data, a growth spurt and pubertal development. This is the fifth case of type II pseudohypoaldosteronism reported in childhood and the first one with hypertension. The beneficial effect of hydrochlorothiazide is underlined.

Diuretic abuse and central pontine myelinolysis.

Patients with eating disorders often use diuretics to eliminate fluid to achieve lower body weight. Diuretic abuse can lead to severe hyponatremia. Central pontine myelinolysis, a disruption of the myelinated neurons of the pons, has been associated with rapid correction of severe hyponatremia. A case is presented of a 35-year-old woman who was brought to the emergency service by ambulance complaining of vomiting for 7 days and that she could not hear well because she was 'worn out'. Initial laboratory values included serum Na 91 mEq/l, K 1.6, Cl 46, bicarbonate 33, BUN 4 mg/dl, glucose 306 mg/dl. After 32 h of intravenous fluids, the serum Na was 126, K 4.0, Cl 89, bicarbonate 25, glucose 118 mg/dl. On the 3rd hospital day the serum Na was 139. On the 4th hospital day she was alert and appropriate. On the 5th hospital day, however, she was confabulating and chatty. The serum Na was 139. She progressed to develop a spastic quadriparesis, speech and swallowing difficulties. A magnetic resonance imaging scan showed central pontine myelinolysis. She acknowledged taking 400 mg daily of furosemide and drinking much water. She had a past history of anorexia nervosa. She had a residual weight phobia and strove to keep her weight below 106 lb. Her height was 5 feet, 6 inches. As illustrated by this case, diuretic abuse can cause severe hyponatremia and the subsequent risk of central pontine myelinolysis. In patients with severe chronic or subacute hyponatremia, a safe restoration rate for serum Na has been less than 0.55 mEq/l/h. Serum Na should be below 135 within the first 48 h and hypernatremia should be avoided.

[Program for interpreting acid-base disorders and assessing blood oxygenation].

The paper describes a program for the interpretation of deviations in the acid-base state (AAS) and the estimation of the blood oxygenation levels. The program was developed for the Iskra-226 microcomputer and is intended for a direct measurement of the gas composition of the blood. The program makes it possible to calculate the AAS and the blood oxygenation levels (20 parameters), to estimate the AAS deviation type and the degree of its compensation, it accumulates and stores the patient data, keeps records of case histories.

Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis: A Case Report and Review of the Literature.

Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid-base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity.Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX.

[Meeting point Stewart. Buffer bases, base excess and strong ions].

Development of a two-buffer model which simulates the acid-base properties of blood and allows comparison of the different acidbase concepts according to Stewart and to Siggaard-Andersen. The two-buffer model consisted of different aqueous solutions of bicarbonate/CO(2) (pCO(2), sCO(2), pK(1)), HEPES buffer (A(tot), pK(a)) and electrolytes. These were used to calculate the pH from the independent variables according to Stewart - strong ion difference (SID), pCO(2) and total concentration of the weak acids (A(tot)) - from which all other dependent variables (cHCO(3)(-), cA(-), BB, BE) were obtained and compared with the measured values. The normal pH (7.408) was calculated from the normal values for SID (48 mmol/l), pCO(2) (40 mmHg) and A(tot) (45.2 mmol/l) and agreed perfectly with the measured value (7.409+/-0.001). This was also valid for all calculated and measured pH values when the SID was varied: non-respiratory alkalosis ( upward arrow) or acidosis ( downward arrow), pCO(2):respiratory acidosis ( upward arrow) or alkalosis ( downward arrow) and A(tot):hyperproteinemic acidosis ( upward arrow) or hypoproteinemic alkalosis ( downward arrow) were varied and the sum of the buffer bases (BB) was always equal to the SID. All changes and hence BE were also equal, providing that A(tot) was normal. This was not the case, however, if A(tot) was outside the normal range, when BE was then the difference from the normal BB at the respective reference point. Whereas the deviation of the measured pCO(2) was acceptable (1.74+/-0.86 mmHg), this was not the case for the SID (-6.18+/-3.58 mmol/l) calculated from the measured ion concentrations (Na, K, Ca, Cl). Despite controversial discussions, both concepts are much closer than might be expected. Whereas in the Stewart approach the focus of analysis is on plasma, with the Siggaard-Andersen approach it is on blood. Hence, a combined analysis of the blood gases (pH, pCO(2), pO(2), sO(2), cHb, BE) and of the strong ion gap (SIG) may be useful.

Cardiotoxicity after massive amantadine overdose.

Amantadine hydrochloride is an antiviral medication used as therapy for parkinsonism and as a cognitive enhancer. We report 2 cases of massive, acute ingestion of amantadine hydrochloride confirmed with serial serum levels. A 47-year-old woman presented to the emergency department (ED) 30 minutes after ingesting 10 g of amantadine (150 mg/kg) by her report. Initial ECG revealed a sinus rhythm with rate of 93 bpm, and a QRS of 84 msec. While in the ED, the patient sustained a pulseless cardiac arrest and the monitor revealed ventricular tachycardia. She was successfully defibrillated. Postdefibrillation ECG showed a sinus rhythm (rate = 82 bpm), QRS of 236 msec, and QTc of 567 msec. The serum potassium was 1.0 mEq/L (1.0 mmol/L). The patient was given 300 ml (300 cc) 3% sodium chloride IV over 10 minutes. Ten minutes after completion of the hypertonic saline infusion, the patient's ECG abnormalities resolved and the QRS was 88 msec. Her potassium was repleted over the next 11 hours postpresentation, and she also received an IV bolus of 4 g of magnesium sulfate immediately after the cardiac arrest. No further hypotension, dysrhythmia, conduction delay, or ectopy was noted during the patient's hospital stay. The second case involved a 33-year-old female patient who presented 1 hour after ingesting 100 tablets of amantadine hydrochloride (100 mg/tab). Initial ECG revealed sinus tachycardia with a QRS of 113 msec, an R wave in lead aVR of 4-5 mm and a QTc of 526 msec. Her serum potassium was 3.0 mEq/L (3.0 mmol/L), her serum calcium was 9.4 mg/dl (2.35 mmol/L), and serum magnesium was 2.1 mg/dl (0.86 mmol/L) on labs drawn at initial presentation. The patient was intubated for airway protection, and her potassium was repleted and corrected over the next 9 hours. Her ECG abnormalities improved 8 hours after initial presentation and normalized at approximately 14 hours postingestion. The patient was discharged home 11 days after her ingestion. Acute amantadine toxicity manifests with life-threatening cardiotoxicity. Concurrent, often profound, hypokalemia may complicate the administration of sodium bicarbonate in the management of cardiac dysrhythmias.

[Diagnosis and treatment of disordered acid-base balance].

Differential diagnosis in disordered acid-base homeostasis is usually possible by measuring the pH, pCO2, pO2 and bicarbonate concentration, and enables differentiation between respiratory alkalosis and acidosis, and metabolic alkalosis and acidosis. Compensatory counter-regulation (respiratory or renal) can make correct assessment of the primary disorder problematic. Treatment of the underlying disease, in particular the provision of adequate oxygenation in respiratory disorders is of the essence. In chronic forms of metabolic acidosis, for example in chronic renal insufficiency and elderly patients, bicarbonate substitution should be initiated in order to prevent the negative effects on various organ systems. Sodium bicarbonate formulations that can be assimilated from the small bowel are especially tolerable and suitable.