We are faced with an anaphylactic reaction to metamizole, in which it is necessary to act quickly or the patient could progress to cardiac arrest. It is important to assess the severity of the allergic reactions, since, in this case, early treatment is essential to prevent high mortality if not applied. The treatment of choice is IM adrenaline (only switch to IV if anaphylaxis is refractory), which has been shown to increase survival, and administration can be repeated every 5-15 minutes if symptoms do not subside. As adjuvant treatment, dexchlorpheniramine could be administered. In this particular case, since the patient was previously treated with propranolol, this indicates that the correct answer is 4, which includes the administration of glucagon, which is administered because patients taking beta-blockers can be resistant to treatment with adrenaline and develop refractory hypotension and prolonged bradycardia. The dose in adults is 1 to 2mg, IV or IM, which can be repeated in 5 minutes or followed by an infusion at 5-15mcg/min.

We are faced with an anaphylactic reaction to metamizole, in which it is necessary to act quickly or the patient could progress to cardiac arrest. It is important to assess the severity of the allergic reactions, since, in this case, early treatment is essential to prevent high mortality if not applied. The treatment of choice is IM adrenaline (only switch to IV if anaphylaxis is refractory), which has been shown to increase survival, and administration can be repeated every 5-15 minutes if symptoms do not subside. As adjuvant treatment, dexchlorpheniramine could be administered. In this particular case, since the patient was previously treated with propranolol, this indicates that [HIDDEN], which includes the administration of glucagon, which is administered because patients taking beta-blockers can be resistant to treatment with adrenaline and develop refractory hypotension and prolonged bradycardia. The dose in adults is 1 to 2mg, IV or IM, which can be repeated in 5 minutes or followed by an infusion at 5-15mcg/min.

A 24-year-old woman with a history of migraine, on propranolol and oral contraceptives, presents with severe dyspnea, hoarseness, rash, nausea and vomiting 30 minutes after taking metamizole. His blood pressure is 90/40 mmHg and SatO2 is 90%. The most correct initial treatment would be to administer:

Adrenaline, dexchlorpheniramine and methylprednisolone.

Adrenaline, dexchlorpheniramine and glucagon.

Successful treatment of severe adrenaline-resistant anaphylactic shock with glucagon in a patient taking a beta-blocker: a case report.

The efficacy of glucagon for adrenaline-resistant anaphylactic shock in patients taking β-blockers is controversial. However, understanding the efficacy of glucagon is important because adrenaline-resistant anaphylactic shock is fatal. We present a case of severe adrenaline-resistant anaphylactic shock in a patient taking a β-blocker, and glucagon was effective in improving hemodynamics. An 88-year-old woman with severe aortic stenosis and taking a selective β-1 blocker underwent transcatheter aortic valve implantation under general anesthesia. Postoperatively, she received 100 mg sugammadex, but 2 min later developed severe hypotension and bronchospasm. Suspecting anaphylactic shock, we intervened by administering adrenaline, fluid loading, and an increased noradrenaline dose. Consequently, the bronchospasm improved, but her blood pressure only increased minimally. Therefore, we administered 1 mg glucagon intravenously, and the hypotension resolved immediately. Glucagon may improve hemodynamics in adrenaline-resistant anaphylactic shock patients taking β-blockers; however, its efficacy must be further evaluated in more cases.

An unusual presentation of anaphylaxis with severe hypertension: a case report.

Low blood pressure and associated postural symptoms are well-recognized manifestations of anaphylaxis. Nonetheless, anaphylaxis can present with high blood pressure and is rarely reported in the literature. We report an unusual presentation of anaphylaxis with severe supine hypertension and orthostatic intolerance. A 43-year-old Asian female presented to the emergency department with generalized itching, hives, and postural dizziness after taking a slow-release diclofenac sodium 100 mg tablet. On admission, the patient was tachycardic with a supine blood pressure of 200/100 mmHg. She had urticaria and bilateral rhonchi. A clinical diagnosis of anaphylaxis was made. She was treated with intravenous hydrocortisone and chlorpheniramine, but intramuscular adrenaline was withheld owing to her high blood pressure. She was kept in the supine position, and her vital parameters were closely monitored. Although the respiratory and cutaneous symptoms improved with treatment, her blood pressure remained elevated. Forty minutes later, the postural dizziness recurred as she sat up on the bed and her blood pressure plummeted from 198/100 mmHg to 80/60 mmHg. She was put back in the supine position immediately, and the blood pressure was restored with three doses of intramuscular adrenaline and a fluid bolus. Her postural symptoms completely resolved after adrenaline, but her blood pressure remained elevated. Two weeks after the initial presentation, a diagnosis of essential hypertension was made, which probably had been undetected. In anaphylaxis, where the cardiovascular system is involved, a blood pressure reduction from baseline is expected in patients with preexisting hypertension. Despite cardiovascular involvement, our patients' blood pressure on presentation to the emergency department was much higher than her pretreatment ambulatory blood pressure, thus making this presentation unusual. Diagnosis and treatment of anaphylaxis can be delayed in patients presenting with high blood pressure. Postural symptoms should alert the clinician to cardiovascular involvement despite elevated supine blood pressure. Early treatment with adrenaline should be considered in these patients with extreme caution.

[Morphine-induced Anaphylaxis before Induction of Anesthesia].

We describe a case of anaphylaxia that occurred in a 67-year-old man. He was planned to have an operation on mitral valve prolapse (MVP) for mitral regurgitation (MR). Morphine 5 mg was injected intramusculaly 45 min before operation. Since then, he felt itchy sensation around his inguinal region. After he came to the operating room, he felt itchy sensation all over the body. Initially, his vatal signs were stable. We started to give extracellular fluid including ulinastatin 300,000 U, methylprednisolone 2 g, and ranitidine 50 mg. A few minutes later, he had nettle rash all over the body and his blood pressure decreased to 40/20 mmHg, and the heart rate increased to 120 beats x min(-1). Soon after, he had pulseless electric activity (PEA). We started chest compression and tracheal intubation. We injected adrenaline 1 mg. After doing the continuous chest compression for 2 min, he revived. He had continuous medications including dopamine 5 μg x kg(-1) x min(-1), dobutamine 5 μg x kg(-1) x min(-1), noradrenaline 0.05 μg x kg(-1) x min(-1). We cancelled the operation, and he was transfered to the high care unit (HCU), where his blood pressure was 120/65 mmHg, and heart rate 120 beats x min(-1). After 24 hours, we extubated his trachea. In this case, morphine was considered to be the most likely cause for anaphylaxis.

Hypertensive Anaphylaxis After Moderna COVID-19 Vaccination: A Case Report.

Hypotension after exposure to an allergen is a well-known indicator of an anaphylactic reaction. However, hypertensive anaphylaxis often goes unrecognized. Increased blood pressure can present as an anaphylactic reaction, which is called hypertensive anaphylaxis. A 48-year-old woman complained of a tickle sensation in the throat and dyspnea 30 minutes after being administered the first dose of the Moderna coronavirus disease 2019 (COVID-19) vaccine. The patient had no history of hypertension, anxiety, or panic disorder. Forty-five minutes after the vaccination, stridor was noted, and the patient developed severe hypertension with a blood pressure of 197/153 mmHg. The patient also had tachycardia, cervical angioedema, and nausea, which occurred in a short period of time, indicating type I hypersensitivity reaction, that is, an anaphylactic reaction. The patient was diagnosed with Brighton classification Level 1 anaphylaxis caused by COVID-19 vaccination. For managing the patient, two intramuscular adrenaline injections, famotidine, chlorpheniramine, metoclopramide, and methylprednisolone were administered via intravenous infusion. After the administration of medications, all symptoms resolved, and the blood pressure was reduced. Other differential diagnoses for increased blood pressure after vaccination were excluded; therefore, we concluded that this phenomenon of increased blood pressure was hypertensive anaphylaxis. Not only hypotension but also the acute onset of increased blood pressure after vaccination may occur as a premonitory symptom of anaphylaxis. In hypertensive anaphylaxis, both anaphylaxis and increased blood pressure can be treated with intramuscular adrenaline injection. Clinicians should be aware of the occurrence of hypertensive anaphylaxis.

Allergic shock and death associated with protamine administration in a diabetic patient.

Insulin is used to treat patients with both type 1 and type 2 diabetes mellitus. Allergic reactions to insulin might be triggered by insulin itself or inactive ingredients in the insulin formulation, including proteins such as protamine in neutral protamine Hagedorn (NPH) insulin. The use of highly purified animal insulin and human recombinant insulin has reduced the incidence of anaphylactic reactions to insulin from ~30% to <1%. We report a case of fatal allergic shock after the administration of protamine in a patient with a history of allergy to fish and a protamine-containing insulin. A 72-year-old Chinese male patient (height, 175 cm; weight, 80 kg) with a history of diabetes and progressive limb weakness was diagnosed with spinal vascular malformations after admission to the Xuan Wu Hospital of Capital Medical University, Beijing, People's Republic of China. He underwent epidural spinal cord arteriovenous fistula embolization with a liquid embolic agent (ethylene vinyl alcohol copolymer) after spinal cord angiography. During the operation, heparin was infused every hour with 6250, 2500, 2500, and 1250 IU, respectively. The last dose of heparin was administered ~10 minutes before the operation was completed. This was followed by the administration of protamine to neutralize the remaining heparin in the patient's body. Blurry vision and dizziness 5 minutes after protamine administration were followed by pruritus and hives over his neck and face. Oxygen was administered and 10 mg of dexamethasone with 2 mg of epinephrine was injected. The patient's heart rate dropped, his blood pressure decreased, and his arterial oxygen saturation (SaO₂) declined progressively. About 10 minutes after the administration of protamine sulfate, the patient developed bradycardic arrest. Cardiopulmonary resuscitation efforts were undertaken and the patient was administered epinephrine 2 mg IV, atropine 0.5 mg IV, and subsequently, intravenous dopamine (50 mg/h). Ten minutes later, the patient's heart rate gradually increased, but blood pressure fluctuated, and SaO₂ ranged from 90% to 100%. Despite the initial response, the patient lost consciousness and heart rate declined progressively within 5 hours. Vasoactive agents including dopamine, norepinephrine, and adrenaline were administered. After all these measures proved ineffectual, the patient died. It was later determined that the patient had a history of allergic reactions to fish as well as to a premixed insulin that contained soluble human insulin 30% and low-protein intensive insulin zinc 70% (NPH). The Naranjo adverse drug reaction probability scale score for the association of protamine with the allergic reaction was 4, suggesting a possible relationship. This case report highlights a preventable fatal allergic reaction possibly associated with protamine administration in a patient with a history of allergy to a protamine-containing insulin.

Thyrotoxic and pheochromocytoma multisystem crisis: a case report.

Thyrotoxic crisis and pheochromocytoma multisystem crisis are rare, life-threatening, emergency endocrine diseases with various clinical manifestations. Here we report a case of a patient who simultaneously developed thyrotoxic crisis and pheochromocytoma multisystem crisis and required intensive cardiovascular management. A 60-year-old Asian man experienced nausea and vomiting, and subsequently developed dyspnea and cold sweats while farming. His serum free thyroxine, free triiodothyronine, and thyrotropin receptor antibody levels were elevated at 2.9 ng/dL, 7.2 pg/dL, and 4.7 IU/L, respectively. Serum thyrotropin levels were suppressed at less than 0.01 μIU/mL. Thyroid echography demonstrated no thyroid swelling (23 × 43 mm). A whole body computed tomography was performed for systemic evaluation. This revealed exophthalmos and a mass of size 57 × 64 mm in the anterior pararenal space. Based on these findings, we made an initial diagnosis of thyrotoxic crisis secondary to exacerbation of Grave's hyperthyroidism. Treatment was begun with an iodine agent at a dose of 36 mg/day, thiamazole at a dose of 30 mg/day, and hydrocortisone at a dose of 300 mg daily for 3 consecutive days. To control tachycardia, continuous intravenously administered propranolol and diltiazem infusions were given. At the same time, small doses of doxazosin and carvedilol were used for both alpha and beta adrenergic blockade. On hospital day 5, his blood pressure and serum catecholamine concentrations (adrenalin 42,365 pg/mL, dopamine 6409 pg/mL, noradrenalin 72,212 pg/mL) were still high despite higher beta blocker and calcium channel blocker doses. These findings contributed to the diagnosis of pheochromocytoma multisystem crisis with simultaneous thyrotoxic crisis. We increased the doses of doxazosin and carvedilol, which stabilized his hemodynamic status. On hospital day 16, metaiodobenzylguanidine scintigraphy showed high accumulation in the right adrenal gland tumor. After retroperitoneal laparoscopic adrenalectomy on hospital day 33, his condition stabilized. He was discharged on hospital day 58. Since he required more intensive cardiovascular management for thyrotoxic crisis, beta blockade was increased under intensive care unit monitoring even though initial alpha blockade is recommended in pheochromocytoma. When these crises occur simultaneously, cardiovascular management can be very challenging.

Allergy -- Treatment / Management

Anaphylaxis treatment begins with triage and the removal from exposure, which can involve decontamination if topical agents are involved or clothing is contaminated. Removal of the patient's clothing and standard precautions by staff such as masks, gloves, and gown should take place. Hand washing by staff who may have used latex gloves or eaten peanuts may be necessary. ABC’s (airway, breathing, and circulation) of emergency care should have priority.  Patients should have oxygen and intravenous administration of fluids. The patient should receive epinephrine intramuscularly (IM) (1 to 1000 dilution {1 mg/1ml} 0.3cc) 0.3 to 0.5 mg which can be repeated every 5 to 15 minutes as needed. Most patients should respond to 1 to 3 doses if symptoms persist, progress or the patient becomes hypotensive IV epinephrine should be started at 0.1 mcg/kg/minute by infusion device and titrated to maintain perfusion of body organs. Patients on beta-blockers should be given glucagon 1 to 5 mg over 5 minutes. Antiemetics should be given to treat vomiting often associated with glucagon administration. Histamine type 2 receptor blockers such as famotidine 20 mg IV or ranitidine at  50 mg IV should be administered. The glucocorticoid, methylprednisolone 125 mg, should be given. [26]

The incidence, aetiology and management of anaphylaxis presenting to an accident and emergency department.

We retrospectively studied anaphylaxis in an A&E department from computerized records. In 1993 (Study A), of 55,000 patients seen in casualty, nine had severe anaphylaxis (ANA) with loss of consciousness (LOC) or fainting (about 1: 6000). Fifteen had generalized allergic reactions (GR) without LOC or fainting, but including dyspnoea due to laryngeal oedema or asthma, angioedema and/or urticaria. Thus there were 24 (about 1:2300) generalized reactions involving hypotension and/or respiratory difficulty. A further case diagnosed as hyperventilation syndrome was probably a wasp sting GR. Six cases of urticaria and/or angioedema were also identified. Of the nine with ANA, a possible cause was identified in eight (3 stings; 2 drugs; 3 foods). There was delay in arrival in A&E: hypotension was noted in three and had resolved spontaneously in six. Only 3/9 were related with adrenaline: i.v. hydrocortisone and chlorpheniramine was the mainstay of treatment. No investigation was recommended nor advice given on future management. Four patients were later referred to our allergy clinic by their GPs. In study B (aug-Oct 1994), nine cases of ANA were identified (1:1500), eight due to bee or wasp stings. The increased incidence was probably related to more detailed history-taking. Only three were treated with adrenaline. The use of adrenaline for future anaphylaxis was discussed with six patients, and five were referred to our allergy clinic. A reaction to the same allergen had occurred previously in 24%. Improved awareness of anaphylaxis and its management is necessary.

Systemic absorption of adrenaline after aerosol, eye-drop and subcutaneous administration to healthy volunteers.

Adrenaline is the drug of choice for management of the anaphylactic reaction. The objective of this study was to compare systemic absorption of adrenaline after administration by different routes to healthy volunteers. Ten puffs (1.5 mg as adrenaline base) with 10-15 s intervals between them followed 2 h later by 20 puffs (3 mg) of adrenaline from a pressurized aerosol (Medihaler-Epi, 3M Riker, 14.0 mg/ml adrenaline acid tartrate) were sprayed into the cheek pouch or inhaled through the mouth or the nostrils. Adrenaline was also administered to the eyes by giving 2 drops (1 mg) of Isopto-Epinal (Alcon, 10 mg X ml-1). Finally, 0.5 ml (0.5 mg) of adrenaline was given subcutaneously in the upper arm of the same individuals. The systemic absorption was determined by measuring plasma adrenaline levels and effects on blood pressure, heart rate and finger tremor before and 5, 15, 30, 60, 90, and 120 min after adrenaline administration. Adrenaline given as eye-drops did not have any significant effect on these parameters. Subcutaneously administered adrenaline caused within 5 min a significant increase of plasma adrenaline level (from 1.0 +/- 0.2 to peak of 6.5 +/- 1.2 nM) which gradually decreased during 2 h. This mode of adrenaline administration increased the systolic blood pressure by a maximum of 11 +/- 3.5 mmHg, heart rate by 9 +/- 2.2 beats X min-1, tremor ratio by 4 +/- 0.6 and reduced the diastolic blood pressure by 18 +/- 4.7 mmHg. The cardiovascular effects were approximately maximum 15 min after administration and lasted almost 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Case Study: 60-Year-Old Female Presenting With Shortness of Breath -- Management -- Endocrine

Considering the primary diagnosis of myxedema coma, early supplementation with thyroid hormone is essential. Healthcare providers followed the American Thyroid Association recommendations, which recommend giving combined T3 and T4 supplementation; however, T4 alone may also be used. T3 therapy is given as a bolus of 5 to 20 micrograms intravenously and continued at 2.5 to 10 micrograms every 8 hours. An intravenous loading dose of 300 to 600 micrograms of T4 is followed by a daily intravenous dose of 50 to 100 micrograms. Repeated monitoring of TSH and T4 should be performed every 1 to 2 days to evaluate the effect and to titrate the dose of medication. The goal is to improve mental function. Until coexistent adrenal insufficiency is ruled out using a random serum cortisol measurement, 50 to 100 mg every 8 hours of hydrocortisone should be administered. In this case, clinicians used hydrocortisone 100 mg IV every 8 hours. Dexamethasone 2 to 4 mg every 12 hours is an alternative therapy.

Endobronchial adrenaline: should it be reconsidered? Dose response and haemodynamic effect in dogs.

Tracheal drug administration is a route for drug delivery during cardiopulmonary resuscitation when intravenous access is not immediately available. However, tracheal adrenaline (epinephrine) injection has been recently shown to be associated with detrimental decrease in blood pressure. This was attributed to exaggerated early beta2 mediated effects unopposed by alpha-adrenergic vasoconstriction. We hypothesized that endobronchial adrenaline administration is associated with better drug absorption, which may abolish the deleterious drop of blood pressure associated with tracheal drug administration. To determine haemodynamic variables after endobronchial adrenaline administration in a non-arrest canine model. Prospective, randomized, laboratory study. Adrenaline (0.02, 0.05, 0.1 mg/kg) diluted with normal saline was injected into the bronchial tree of five anaesthetized dogs. Injection of 10-ml saline served as control. Heart rate, blood pressure and arterial blood gases were monitored for 60 min after drug instillation. The protocol was repeated after 1 week. Adrenaline at a dose of 0.02 mg/kg produced only a minor initial decrease in diastolic (from 90 +/- 5 to 78 +/- 3 mmHg, P=0.05), and mean blood pressure (from 107 +/- 4 to 100 +/- 3 mmHg, P=0.05), in all dogs. This effect lasted less then 30 s following the drug administration. In contrast, higher adrenaline doses (0.05 and 0.1 mg/kg) produced an immediate increase in diastolic (from 90 +/- 5 to 120 +/- 7 mmHg; and from 90 +/- 5 to 170 +/- 6 mmHg, respectively), and mean blood pressure (from 107 +/- 4 to 155 +/- 10 mmHg; and from 107 +/- 4 to 219 +/- 6 mmHg, respectively). All adrenaline doses resulted in an immediate increase in systolic blood pressure and pulse. Endobronchial administration of saline (control) affected none of the haemodynamic variables. In a non-arrest model, endobronchial adrenaline administration, as opposed to the effect of tracheal adrenaline, produced only a minor decrease in diastolic and mean blood pressure. We suggest that endobronchial adrenaline administration should be investigated further in a CPR low-flow model when maintaining adequate diastolic pressure may be crucial for survival.

Adrenaline and stress-induced increases in blood pressure in rats.

Stress was induced by immobilizing the hind limbs of rats for 12 days and housing the rats in individual cages. Control rats were housed in groups without immobilization. Blood pressure and heart rate were measured through an indwelling carotid cannula. After 10 and 12 days of immobilization and isolation, the stressed rats had significantly higher blood pressures (ca. 10 mmHg) and higher cardiac adrenaline levels (ca. 90%). After adrenal medullectomy cardiac adrenaline levels were markedly reduced in both stressed and control rats. Furthermore, the stressing procedure did not cause a rise in blood pressure in adrenal-medullectomized rats. Desipramine HCl (2 mg/kg per day), administered orally to block the neuronal uptake of adrenaline, prevented the elevation in blood pressures and cardiac adrenaline levels. Propranolol HCl (2.8 mg/kg per day), orally, also prevented the rise in blood pressure. The results are consistent with the hypothesis that activation of facilitatory prejunctional beta-adrenoceptors on sympathetic nerves by neuronally-released adrenaline may be responsible for the raised blood pressure.

Angiotensin Converting Enzyme Inhibitor-related Angioedema: A Case of an Unexpected Death.

Angioedema is an asymmetric non-pitting oedema on face, lips, tongue and mucous membranes; any delay in diagnosis and treatment can be fatal. Treatment with lisinopril as an angiotensin converting enzyme (ACE) inhibitor, can be a reason of angioedema. Here we report a case who developed oral-facial edema four years after using lisinopril/hydrochlorothiazide. Laryngeal oedema is a main cause of death in angioedema. The treatment of choice in angioedema including fresh frozen plasma, C1 inhibitor concentrations and BRK-2 antagonists (bradykinin B2 receptor antagonists) were used. In this case; a 77 years old female patient suffering from hypertension was considered. This patient was suffering two days from swelling on her face and neck. Non- allergic angioedema was distinguished in five major forms; acquired (AAO), hereditary (HAE), renin-angiotensin-aldosterone system (RAAS) blocker-dependent, pseudoallergic angioedema (PAS) and an idiopathic angioedema (IAO). She was admitted to our clinic with the diagnosis of hereditary angioedema. Patient had skin edema and life threatening laryngeal edema. In emergency department treatment was started using intravenous methylprednisolone, diphenydramine as well as inhaled and subcutaneous epinephrine simultaneously. Despite the initial treatment, the patient died due to the insufficient respiration and cardiac arrest. The patient has no history of kidney disease.

Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality.

Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan. Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.

Pharmacological prevention of serious anaphylactic reactions due to iodinated contrast media: systematic review.

To review the efficacy of pharmacological prevention of serious reactions to iodinated contrast media. Systematic review. Systematic search (multiple databases, bibliographies, all languages, to October 2005) for randomised comparisons of pretreatment with placebo or no treatment (control) in patients receiving iodinated contrast media. Review methods Trial quality was assessed by all investigators. Information on trial design, population, interventions, and outcomes was abstracted by one investigator and cross checked by the others. Data were combined by using Peto odds ratios with 95% confidence intervals. Nine trials (1975-96, 10 011 adults) tested H1 antihistamines, corticosteroids, and an H1-H2 combination. No trial included exclusively patients with a history of allergic reactions. Many outcomes were not allergy related, and only a few were potentially life threatening. No reports on death, cardiopulmonary resuscitation, irreversible neurological deficit, or prolonged hospital stays were found. In two trials, 3/778 (0.4%) patients who received oral methylprednisolone 2x32 mg or intravenous prednisolone 250 mg had laryngeal oedema compared with 11/769 (1.4%) controls (odds ratio 0.31, 95% confidence interval 0.11 to 0.88). In two trials, 7/3093 (0.2%) patients who received oral methylprednisolone 2x32 mg had a composite outcome (including shock, bronchospasm, and laryngospasm) compared with 20/2178 (0.9%) controls (odds ratio 0.28, 0.13 to 0.60). In one trial, 1/196 (0.5%) patients who received intravenous clemastine 0.03 mg/kg and cimetidine 2-5 mg/kg had angio-oedema compared with 8/194 (4.1%) controls (odds ratio 0.20, 0.05 to 0.76). Life threatening anaphylactic reactions due to iodinated contrast media are rare. In unselected patients, the usefulness of premedication is doubtful, as a large number of patients need to receive premedication to prevent one potentially serious reaction. Data supporting the use of premedication in patients with a history of allergic reactions are lacking. Physicians who are dealing with these patients should not rely on the efficacy of premedication.

[Vasoplegic syndrome after cardiac surgery with cardiopulmonary bypass].

A 71-year-old valvular patient with cardiac arrhythmia, low ejection fraction, administered angiotensin converting enzyme inhibitor underwent aortic and mitral valvular replacement. Starting during normothermic cardiopulmonary bypass (CPB), hypotension occurred, refractory to phenylephrine, noradrenaline, terlipressin, hydrocortisone and dexchlorpheniramine. After 3 hr of CPB biventricular hyperkinesia, severe hypotension and metabolic acidosis persisted despite volume loading, sodium bicarbonate, adrenaline infusion and intraaortic conterpulsation. Refractory asystole occurred 5 hr postoperatively. The responsability of sepsis and anaphylaxis were ruled out and post-CPB vasoplegic syndrome appeared to be involved. Moderate and severe vasoplegic syndromes are discussed with regards to risk factors, physiology and treatment, including prophylaxis with vasopressin and methylene blue.

Anaphylactic Shock as a Rare Side Effect of Intravenous Amiodarone.

Amiodarone is a very commonly used antiarrhythmic agent. However, it has a wide variety of systemic side effects as well as many hypersensitivity and allergic reactions, ranging from angioedema to anaphylactic shock in patients who have iodine allergies. We present a rare and unique case of an 86-year-old female who developed anaphylactic shock from intravenous (IV) amiodarone. She had no reported allergies to iodine or iodinated contrast. She had a history of chronic persistent atrial fibrillation and was being maintained on oral amiodarone as an outpatient. She was admitted with shortness of breath and was found to have atrial fibrillation with rapid ventricular response. She was started on an IV amiodarone bolus. Immediately after a few milliliters of infusion, she complained of shortness of breath, with facial flushing and generalized blanching erythema, followed by severe hypotension and cardiopulmonary arrest. IV amiodarone infusion was suspected to be the culprit and was discontinued immediately. IV epinephrine 0.3 mg was administered, followed by the advanced cardiovascular life support (ACLS) protocol for cardiopulmonary arrest. She did not respond to the standard ACLS protocol and continued to remain in cardiopulmonary arrest. A spot diagnosis of anaphylactic reaction to IV amiodarone was made, and she was started on IV epinephrine infusion 0.1 µg/kg/minute, and immediate return of spontaneous circulation was achieved. She was started on IV methylprednisolone 125 mg, IV famotidine 20 mg, and IV diphenhydramine 25 mg. She was intubated and required mechanical ventilation. She was successfully extubated later and safely discharged, receiving oral metoprolol 25 mg for rate control and PO rivaroxaban 20 mg once daily. Anaphylactic shock from IV amiodarone administration is a potentially fatal complication observed in patients with prior reported allergies to iodine or iodinated contrast media. It has rarely been reported in the absence of prior allergy to iodine or iodinated contrast media. Prompt recognition by clinicians is prudent for early diagnosis and appropriate treatment.

An immediate generalized reaction to iopamidol.

Intravascularly administered lower-osmolality contrast media cause fewer adverse effects than do higher-osmolality media. Immediate generalized reactions such as acute urticaria or bronchospasm have been documented occasionally in patients receiving lower-osmolality contrast media. To our knowledge, this is the first reported case of an immediate generalized reaction to a lower-osmolality contrast medium in which significant hypotension also occurred. During cardiac catheterization, in a patient who had never been exposed to a contrast medium, a 69-year old man developed chest tightness, periorbital and facial edema, slight uvular edema, and a decline in blood pressure from 150/71 to 97/67 mm Hg. Epinephrine hydrochloride, diphenhydramine hydrochloride, and hydrocortisone were administered. The lack of absolute safety of lower-osmolality contrast media emphasizes the need for clinical awareness and availability of emergency therapy when these agents are utilized.

Addition of glucagon to adrenaline improves hemodynamics in a porcine model of prolonged ventricular fibrillation.

Cardiac arrest is a daunting medical emergency. The aim of the present study was to assess whether the combination of adrenaline and glucagon would improve initial resuscitation success, 48-hour survival, and neurologic outcome compared with adrenaline alone in a porcine model of ventricular fibrillation. Ventricular fibrillation was induced in 20 healthy Landrace/Large White piglets, which were subsequently left untreated for 8 minutes. The animals were randomized to receive adrenaline alone (n = 10, group C) and adrenaline plus glucagon (n = 10, group G). All animals were resuscitated according to the 2010 European Resuscitation Council guidelines. Hemodynamic variables were measured before arrest, during arrest and resuscitation, and during the first 60 minutes after return of spontaneous circulation. Survival and a neurologic alertness score were measured at 48 hours after return of spontaneous circulation. Return of spontaneous circulation was achieved in 8 animals (80%) from group C and 10 animals (100%) from group G (P = .198). A significant gradual increase in coronary perfusion pressure and diastolic aortic pressure over time, which started 1 minute after the onset of cardiopulmonary resuscitation, was observed. Three animals (30%) from group C and 9 animals (90%) from group G survived after 48 hours (P = .006), whereas neurologic examination was significantly better in the animals of group G (P < .001). In this porcine model of prolonged ventricular fibrillation, the addition of glucagon to adrenaline improves hemodynamics during resuscitation and early postresuscitation period and may increase survival.

InternalMed_Harrison

Therapy is directed at reversing the histamine effect with antihistamines, either H-1 or H-2. If bronchospasm is severe, an inhaled bronchodilator—or in rare, extremely severe circumstances, injected epinephrine—may be used. Glucocorticoids are of no proven benefit. Protracted nausea and vomiting, which may empty the stomach of toxin, may be controlled with a specific antiemetic, such as ondansetron or prochlorperazine. The persistent headache of scombroid poisoning may respond to cimetidine or a similar antihistamine if standard analgesics are not effective.

Interventions for pityriasis rosea.

Pityriasis rosea is a scaly rash that mainly affects young adults. It can be very itchy but most people recover within 2 to 12 weeks. To assess the effects of interventions for pityriasis rosea. We searched the Cochrane Skin Group Specialised Register (December 2004), the Cochrane Central Register of Controlled Clinical Trials in The Cochrane Library (Issue 4, 2004), MEDLINE (1966 to January 2005), EMBASE (1976 to January 2005), LILACS (1982 to January 2005), BIOSIS Preview (1980 to June 2002), and ongoing trials databases. We scanned bibliographies of published studies, abstracts from dermatology conference proceedings, corresponded with trialists and contacted the pharmaceutical industry. Randomised controlled trials evaluating interventions for pityriasis rosea. Two authors independently assessed trial quality and extracted data. We contacted study authors to retrieve missing data. Three trials involving 148 people were included. One poor quality trial (23 people), compared intravenous glycyrrhizin and intravenous procaine. It found no significant difference between the two interventions for treating symptoms and rash. One fair quality trial (85 people), compared the oral antihistamine dexchlorpheniramine (4 mg), the oral steroid betamethasone (500 mcg), and a combination of betamethasone (250 mcg) and dexchlorpheniramine (2 mg). It found no significant difference in itch resolution at two weeks, as rated by the participants, between dexchlorpheniramine and betamethasone, and the combination of dexchlorpheniramine and betamethasone. However, both dexchlorpheniramine and betamethasone alone seem to be better at clearing rash than the combination of dexchlorpheniramine and betamethasone. These interventions were not compared with placebo. The small good quality trial (40 people) that compared oral erythromycin and placebo found that erythromycin was more effective than placebo in terms of rash improvement, as rated by the trialists, after two weeks (RR 13.00; 95% CI 1.91 to 88.64). It was also more effective in decreasing the itch score (difference of 3.95 points, 95% CI 3.37 to 4.53). No serious adverse effects were reported for the interventions. Two out of 17 people on oral erythromycin and 1 out of 17 on placebo reported minor gastrointestinal upset. We found inadequate evidence for efficacy for most treatments for pityriasis rosea. Oral erythromycin may be effective in treating the rash and decreasing the itch. However, this result should be treated with caution since it comes from only one small RCT. More research is necessary to evaluate the efficacy of erythromycin and other treatments.

Celecoxib-associated anaphylaxis.

To report and discuss a case of anaphylaxis in a young, healthy white male taking celecoxib for intermittent lower back pain. A healthy 27-year-old man with a documented history of anaphylaxis to penicillins and macrolides presented to the emergency department (ED) in anaphylactic shock after ingesting a 200-mg capsule of celecoxib and a cup of orange juice. The patient had been taking celecoxib over the past 6 months, for 1-2 weeks at a time, for low back pain secondary to a pilonidal cyst and an L5/S1 bulging disc. The day of admission was the seventh day of the most recent course of twice-daily celecoxib. The patient initially self-treated the reaction with diphenhydramine and subcutaneous epinephrine that he had at home due to his history of drug- and bee sting-induced anaphylaxis; neither intervention improved his symptoms. He became profoundly diaphoretic and developed systemic swelling, shortness of breath, bradycardia, and hypotension. Emergency medical services transported the patient to the ED, where he was treated appropriately and the symptoms resolved. However, 4 hours later, at time of discharge from the ED, the symptoms recurred. He was admitted to the intensive care unit and monitored for 3 days. Supportive care, steroids, and histamine blockade provided resolution of the symptoms. Cardiac workup was initiated because of the recurrence and severity of bradycardia and hypotension; results of the workup were unremarkable. The patient was discharged in stable condition. This case demonstrates rare anaphylaxis to celecoxib in a patient who had previously taken the drug and who had documented tolerance to sulfonamide antibiotics. Despite this history, our patient developed type V immunoglobulin E-mediated anaphylaxis secondary to the sulfonamide component of celecoxib. This reaction was considered probable according to the Naranjo probability scale. A review of published case reports and related allergy literature for celecoxib allergenicity revealed that such reactions are rare. This is the first case report with great detail of a patient with anaphylaxis to celecoxib after having previously tolerated the medication. Celecoxib can produce an anaphylactic reaction in patients who have previously tolerated sulfonamide antibiotics and who have previously tolerated celecoxib. This case also reviews the potentially biphasic presentation of anaphylaxis. Clinicians need to be aware of this biphasic anaphylactic response to ensure optimal duration of evaluation.

Hypersensitivity to administered adrenaline in tetraplegia.

Case report. To describe two clinical examples of denervation hypersensitivity, an enhanced response to catecholamines demonstrated experimentally in tetraplegic patients. USA. A 63-year-old man with chronic paralysis at C4 ASIA Impairment Scale (AIS) A with partial preservation to T6, and a history of coronary artery and pulmonary disease, developed bradycardia leading to cardiac arrest. He was treated with intravenous atropine 0.4 mg and adrenaline 1 mg. He regained consciousness and blood pressure within 30 s, but developed supraventricular tachycardia leading to ventricular fibrillation and death within minutes. The dose of adrenaline was routine for a cardiac arrest.A 60-year-old man with chronic paralysis at C6, AIS A, presented with fever to 106 degrees F and a renal stone. Thirty minutes after treatment with intravenous fluids, antibiotics, and 1 g aspirin orally, he became afebrile, then suddenly lost consciousness and palpable pulse. He recovered with equal rapidity after an intravenous injection of 0.1 mg adrenaline. The dose of adrenaline was a tenth the usual dose for cardiac arrest. Because of denervation hypersensitivity, effective treatment of a cardiac arrest in tetraplegic patients may require a reduced dose of adrenaline.

[A case of anaphylactic shock in an elderly man following protamine sulfate administration during emergent off-pump coronary artery bypass grafting].

An 80-year-old diabetic man undergoing emergent off-pump coronary artery bypass grafting for acute myocardial infarction developed anaphylactic shock immediately following administering a small dose of protamine sulfate. Preoperative examination revealed atrial fibrillation, severe three-vessel coronary artery disease and impaired left ventricular function with ejection fraction of 40% and severe septal as well as apical hypokinesis and akinesis. After successful completion of coronary bypass grafting, a total of 40 mg of protamine sulfate was given through the central venous line. Three minutes after protamine administration, profound hypotension occurred. Pulmonary artery pressure was low and the left ventricle was almost empty by transesophageal echocardiography. Hypotension was refractory to rapid administration of 2 l of crystalloid and albumin, and repeated administrations of phenylephrine. Blood pressure finally returned towards baseline after infusion of norepinephrine 0.2 microg x kg(-1) x min(-1) and epinephrine 0.1 microg x kg(-1) x min(-1). Hemoconcentration and impaired oxygenation were also noted. The situation suggested anaphylactic shock due to protamine. He had diabetes mellitus for 20 years and been treated by protamine containing insulin. Postoperative interview revealed that the patient had experienced urticaria over the abdominal area with neutral protamine hagedorn (NPH) insulin administration. This history suggested that the patient had been sensitized by protamine before surgery. Although it is rare to experience anaphylactic shock due to protamine, it is important to elicit the detailed allergic history to insulin in diabetic patients. Because anaphylactic shock still carries high mortality even in a patient without cardiac disease, we were lucky to save this elderly patient with acute myocardial infarction and compromised left ventricular function.

Efficacy of Intravenous, Endotracheal, or Nasal Adrenaline Administration During Resuscitation of Near-Term Asphyxiated Lambs.

<bObjectives:</b Neonatal resuscitation guidelines recommend administering intravenous (IV) adrenaline if bradycardia persists despite adequate ventilation and chest compressions (CC). Rapid IV access is challenging, but little evidence exists for other routes of administration. We compared IV, endotracheal (ET), and intranasal routes for adrenaline administration during resuscitation of asphyxiated newborn lambs. <bStudy design:</b Near-term lambs (<in</i = 22) were delivered by caesarean section. Severe asphyxia was induced by clamping the umbilical cord while delaying ET ventilation until blood flow in the carotid artery ceased. Following a 30 s sustained inflation and ventilation for 30 s, we commenced uncoordinated CC at 90/min. We randomized four groups receiving repeated treatment doses (Tds) every 3rd min of (i) IV-Adrenaline (50 μg), (ii) ET-Adrenaline (500 μg), (iii) Nasal-Adrenaline via an atomizer (500 μg), and (iv) IV-saline. If return of spontaneous circulation (ROSC) was not achieved after three Tds by the assigned route, up to two rescue doses (Rds) of IV adrenaline were administered. Main outcome measures were achievement of ROSC and time from start of CC to ROSC, defined as heart rate >100/min, and mean carotid arterial pressure >30 mmHg. <bResults:</b In the IV-Adrenaline group, 5/6 lambs achieved ROSC after the first Td, whereas 1 lamb required two Tds before achieving ROSC. In the ET-Adrenaline group, 1/5 lambs required one Td, 1 lamb required three Tds, 2 lambs required 2 Rds, and 1 did not achieve ROSC. In the Nasal-Adrenaline group, 1/6 lambs required one Td, 2 required two Tds, whereas 3 lambs required either one (2 lambs) or two (1 lamb) Rds of adrenaline to achieve ROSC. In the IV-saline group, no lambs achieved ROSC until adrenaline Rds; 4/5 lambs required one Rd and 1 lamb required two Rds. Time to ROSC was shorter using IV-Adrenaline (2.4 ± 0.4 min) compared with ET-Adrenaline (10.3 ± 2.4 min), Nasal-Adrenaline (9.2 ± 2.2 min), and IV-saline (11.2 ± 1.2 min). <bConclusion:</b IV adrenaline had superior efficacy compared with nasal or ET administration. Nasal administration had a similar effect as ET administration and is an easier route for early application. Nasal high-dose adrenaline administration for neonatal resuscitation merits further investigation.

Drug-induced hypoglycemia. A review of 1418 cases.

The present review catalogues 1418 reported cases of drug-induced hypoglycemia. The main findings are that sulfonylureas (especially chlorpropamide and glyburide), either alone or with a second hypoglycemic or potentiating agent, still account for 63% of all cases; that alcohol, propranolol, and salicylate, either singly or with another hypoglycemic drug, are the next most frequent offenders (19% of the total); and that one older drug (quinine) and three new ones (pentamidine, ritodrine, and disopyramide) have caused an additional 7% of all episodes of severe hypoglycemia. The clinical factors that set the stage for drug-induced hypoglycemia are still restricted food intake, age, hepatic disease, and renal disease, both individually and even more so in combination. Drug-induced hypoglycemia continues to be so common that virtually every unconscious patient should be considered hypoglycemic until immediate estimation of the blood sugar level rules it in or out. If ruled in, the clinician should promptly start 10% intravenous glucose and plan to maintain it uninterruptedly for 1 or more days, with added glucagon, hydrocortisone, and diazoxide administration if necessary, until sustained hyperglycemia guarantees that all drug effects have worn off.

Haemodynamic effects of tracheally administered adrenaline in anaesthetised patients.

Ten patients undergoing arterial surgery in the leg received a combined general anaesthetic, which included muscle relaxation and intubation of the trachea, and a regional anaesthetic using a lumbar extradural catheter. The radial arterial pressure was measured. Adrenaline 0.1 micrograms.kg-1 was administered intravenously and the heart rate, arterial pressure and oxygen saturation were recorded every 15 s for 10 min. Adrenaline in 5 ml of saline was given into the trachea at 10 min intervals. The first was saline only, and successive injections contained 0.5 micrograms.kg-1, 1 microgram.kg-1, 2 micrograms.kg-1, and 3 micrograms.kg-1 of adrenaline. The mean maximum rise in systolic arterial pressure after adrenaline given intravenously was 30 (SD 11) mmHg, and 15 (SD 16) mmHg after the maximum dose of adrenaline given into the trachea (p < 0.05). The mean systolic arterial pressure was significantly increased between 45 s and 4.5 min after the adrenaline given intravenously, and 2 min after adrenaline given into the trachea. Of seven patients who received adrenaline 3 micrograms.kg-1 into the trachea, six had no noticeable effect and in the other patient, the increase in arterial pressure was less than 90% of the maximum rise after the adrenaline. We conclude that adrenaline given into the trachea is unreliable in humans with very large doses necessary in some patients to produce a clinically useful haemodynamic effect.

[A fatal case of hereditary angioedema].

A 27 year old woman suffered from recurrent attacks of laryngeal oedema due to C1-inhibitor deficiency, and was treated with danazol and tranexamic acid. The trachea was intubated with great difficulty, twice on one occasion. Two and a half years later she was admitted to the Intensive Care Unit with dyspnoea and dysphagia. Tranexamic acid, corticosteroids, adrenaline (also inhalated), were administered intravenously, but dyspnoea progressed. During preparation for tracheostomy the patient suffered from sudden airway collapse. Attempts to ventilate by mask, puncture of the cricothyroid membrane and intubation were unsuccessful. A small tube was eventually inserted into the trachea after four minutes. The patient was then severely cyanotic with a pulse of thirty, and had dilated pupils. The next morning convulsions ensued and a CT scan showed cerebral oedema. In spite of treatment with pentothal, mannitol and hyperventilation she died. The authors advocate the use of intravenous infusion of C1-inhibitor concentrate, since traditional treatment is inadequate. Persons with hereditary angio-oedema should have a personal supply of C1-inhibitor at hand.

Experimental cardiac arrest treatment with adrenaline, vasopressin, or placebo.

The effect of vasoconstrictors in prolonged cardiopulmonary resuscitation (CPR) has not been fully clarified. To evaluate adrenaline and vasopressin pressure effect, and observe the return of spontaneous circulation (ROSC). A prospective, randomized, blinded, and placebo-controlled study. After seven minutes of untreated ventricular fibrillation, pigs received two minutes cycles of CPR. Defibrillation was attempted (4 J/kg) once at 9 minutes, and after every cycle if a shockable rhythm was present, after what CPR was immediately resumed. At 9 minutes and every five minutes intervals, 0.02 mg/kg (n = 12 pigs) adrenaline, or 0.4 U/kg (n = 12) vasopressin, or 0.2 mL/kg (n = 8) 0.9% saline solution was administered. CPR continued for 30 minutes or until the ROSC. Coronary perfusion pressure increased to about 20 mmHg in the three groups. Following vasoconstrictors doses, pressure level reached 35 mmHg versus 15 mmHg with placebo (p < 0.001). Vasopressin effect remained at 15-20 mmHg after three doses versus zero with adrenaline or placebo. ROSC rate differed (p = 0.031) among adrenaline (10/12), vasopressin (6/12), and placebo (2/8). Time-to-ROSC did not differ (16 minutes), nor the number of doses previously received (one or two). There was no difference between vasoconstrictors, but against placebo, only adrenaline significantly increased the ROSC rate (p = 0.019). The vasoconstrictors initial pressure effect was equivalent and vasopressin maintained a late effect at prolonged resuscitation. Nevertheless, when compared with placebo, only adrenaline significantly increased the ROSC rate.

Allergy -- Treatment / Management

Weight-base dosing is recommended for pediatric patient populations. IM epinephrine is dosed at 0.01mg/kg and injected in the outer thigh. The maximum dose for children over 50 kg is 0.5 mg; this is done every 5 to 15 minutes for up to three doses if needed until obtaining an adequate response. After three doses, IV administration should begin 0.1 to 1 mcg/kg/minute titrated to effect. IV fluids should be 10 to 20 ml/kg infusion for hypotension and fluid replacement. H1 histamine blockers should be dosed at 1 mg/kg for diphenhydramine up to a maximum of 40 mg. H2 histamine blockers ranitidine is 1 mg/kg up to 50 mg and famotidine at 0.25 mg /kg iv not to exceed 40mg/day for patients 1 to 16 years of age. (If labs show renal dysfunction, consultation with the pharmacy is recommended for dosing based on creatinine clearance in both pediatrics and adults). Glucocorticoid administration methylprednisolone is 1 mg/kg up to a max of 125 mg. [1] [26]

Hemodynamic changes by drug interaction of adrenaline with chlorpromazine.

Adrenaline (epinephrine) is included in dental local anesthesia for the purpose of vasoconstriction. In Japan, adrenaline is contraindicated for use in patients receiving antipsychotic therapy, because the combination of adrenaline and an antipsychotic is considered to cause severe hypotension; however, there is insufficient evidence supporting this claim. The purpose of the present study was to clarify the changes in hemodynamics caused by drug interaction between adrenaline and an antipsychotic and to evaluate the safety of the combined use of adrenaline and an antipsychotic in an animal study. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. A catheter was inserted into the femoral artery to measure blood pressure and pulse rate. Rats were pretreated by intraperitoneal injection of chlorpromazine or chlorpromazine and propranolol, and after 20 minutes, saline or 1 of 3 different doses of adrenaline was administered by intraperitoneal injection. Changes in the ratio of mean arterial blood pressure and pulse rate were measured after the injection of adrenaline. Significant hypotension and tachycardia were observed after the injection of adrenaline in the chlorpromazine-pretreated rats. These effects were in a dose-dependent manner, and 100 μg/kg adrenaline induced significant hemodynamic changes. Furthermore, in the chlorpromazine and propranolol-pretreated rats, modest hypertension was induced by adrenaline, but hypotension and tachycardia were not significantly shown. Hypotension was caused by a drug interaction between adrenaline and chlorpromazine through the activation of the β-adrenergic receptor and showed a dose-dependent effect. Low-dose adrenaline similar to what might be used in human dental treatment did not result in a significant homodynamic change.

Case report: acute unintentional carbachol intoxication.

Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.