Michael McGuigan

Management of Anaphylactoid Reactions to Intravenous N-Acetylcysteine

STUDY OBJECTIVE To develop management guidelines for the treatment of anaphylactoid reactions to intravenous N-acetylcysteine (NAC) and to assess the safety of restarting the infusion after a reaction. METHODS In phased 1, we used a 6-year retrospective case series of hospitalized patients and a review of the literature to develop the management guidelines for anaphylactoid reactions to intravenous NAC. In phase 2, these guidelines were evaluated prospectively in our poison-control center. RESULTS In phase 1, the charts of 11 patients with anaphylactoid reactions (9 cutaneous and 2 systemic) were reviewed. In most cases, no treatment or treatment with diphenhydramine alone or with salbutamol was sufficient to continue or restart NAC infusion safely. On the basis of our findings in those patients and on published experience, we concluded that anaphylactoid reactions to intravenous NAC are dose-related and the antihistamines are useful in controlling and in preventing recurrence of anaphylactoid symptoms. We developed the following guidelines: flushing requires no treatment, urticaria should be treated with diphenhydramine, and NAC infusion should be continued in both cases. Angioedema and respiratory symptoms each require the administration of diphenhydramine and symptomatic therapy. In these cases, NAC infusion should be stopped but, when necessary, can be started 1 hour after the administration of diphenhydramine in the absence of symptoms. In phase 2, 50 patients (31 cutaneous and 19 systemic reactions) were treated prospectively with the use of these guidelines. Recurrence of symptoms occurred in only one case involving a deviation from the guidelines. The NAC infusion was restarted immediately after the administration of diphenhydramine in a patient who sustained a systemic reaction. CONCLUSION Non-life-threatening anaphylactoid reactions to intravenous NAC are treated easily and the infusion may be continued or restarted safely after the administration of diphenhydramine.

Acute Renal Dysfunction in Acetaminophen Poisoning

Although acetaminophen (APAP)-associated liver injury is well recognized, there are few reports describing APAP nephrotoxicity, and most of them are single cases. It has also been suggested that N-acetylcysteine (NAC), used to treat the hepatotoxicity, may be harmful to the kidneys. To examine this contention and to determine whether renal involvement in APAP poisoning is at all common, we analyzed the incidence and outcome of acute renal dysfunction in patients hospitalized for APAP overdose reported to our regional poison center over a year. Eleven APAP-poisoned patients had elevated liver function tests; nine of them had azotemia. Those with higher AST levels tended to be younger and to have lower APAP levels on admission. Two patients with acute renal injury died after admission. The other seven patients with renal dysfunction recovered in 2 to 7 days. Six of these received NAC; their mean serum creatinine fell from 3.2 ± 2.0 versus 1.7 ± 0.9 mg/dL (p < 0.05). We conclude that acute renal failure is not uncommon in APAP poisoning and appears to be unrelated to the degree of liver injury. NAC therapy did not seem to worsen nephrotoxicity.

Deferoxamine (desferrioxamine). New toxicities for an old drug.

SummaryIron is an esssential element for body homoeostasis, but there is no effective mechanism for elimination of an excess of this mineral. Deferoxamine (desferrioxamine) is currently the treatment of choice for iron overload states from both acute iron intoxication and transfusion-dependent anaemias. The pharmacokinetics of deferoxamine are confounded both by its ability to chelate endogenous and exogenous iron and by the laboratory techniques used for its determination. Its iron-complex (ferrioxamine) has different pharmacokinetic properties. Because of its effectiveness, the use of deferoxamine is becoming more common, involving long term and high dose regimens. As a result of this, more and more toxicities that were not known in the past have been described and characterised. The most serious of these include hypotension, renal insufficiency, neurotoxicity, growth retardation and opportunistic infections; some of these side effects may be attributed to or aggravated by ferrioxamine. The pharmacological and toxicological literature on deferoxamine, and possible mechanisms for its toxicity, are reviewed and discussed.

Lithium poisoning from a poison control center perspective

The purpose of this study was to evaluate the severity of lithium poisoning from a poison control center–based population and the correlation of the Hansen and Amdisen classification with outcome and lithium levels in that setting. All lithium overdoses brought to the attention of the poison control center were prospectively observed during 1 year. Demographic data, amount ingested, coingestants, symptoms and signs, lithium levels, treatment, and outcome were recorded. There were 12 acute lithium overdoses: 5, 5, and 2 with grade 0, 1, and 2, respectively. No patients required hemodialysis or had sequelae or died. There were 174 acute-on-chronic overdoses: 66, 85, 15, and 8 with grade 0, 1, 2, and 3, respectively. Six patients underwent hemodialysis; none had sequelae but one died. There were 19 chronic poisonings: 9, 9, and 1 with grade 1, 2, and 3, respectively. Three patients underwent hemodialysis; one had sequelae and one died. Patients classified as grade 2 had higher lithium levels than those with grade 1 in patients with only lithium poisoning (3.08 ± 0.77 vs. 2.09 ± 0.91 mmol/L P = 0.03).The study concluded that morbidity (0.5%) and mortality (1%) associated with lithium poisoning are rarely observed. The Hansen and Amdisen classification does not appear to be a useful clinical tool to predict either morbidity or mortality and does not correlate well with lithium levels.

Carbamazepine Interference with an Immune Assay for Tricyclic Antidepressants in Plasma

BACKGROUND Drug toxicological screening is commonly used as a diagnostic tool in patients with suspected toxic ingestion. False positive results due to cross-reactive compounds in drug assays may lead to misdiagnosis and mismanagement, especially when child abuse is suspected. CASE REPORT Two of our patients with history of ingestion of carbamazepine were tested positive on screening with the tricyclic antidepressant immunoassay. The immunoassays known cross-reactivity for carbamazepine is reportedly as low as 0.3%. Plasma samples of our patients were initially considered positive for tricyclic antidepressants because the cross-reaction of carbamazepine gave tricyclic antidepressant concentrations as imipramine equivalent sufficiently above the assay cut-off point (20 ng/mL). Later, confirmatory urine testing of both patients using high-performance liquid chromatography was negative for tricyclic antidepressants. CONCLUSION This interference has significant clinical implications, and can be avoided on urine testing using a specific chromatographic assay such as high-performance liquid chromatography.

Acute digoxin overdose in a newborn with renal failure: use of digoxin immune Fab and peritoneal dialysis.

Digitalis intoxication is a common problem, mainly because of the narrow margin of safety of digoxin. These patients may have concomitant renal failure. In patients who have renal failure and who have been treated with digoxin-Fab, the elimination of the digoxin-Fab complex is significantly delayed, and there is a risk of dissociation of the complex with rebound of free digoxin and recurrence of toxicity. The high molecular weight of digoxin and digoxin-Fab complex prevents its elimination by hemodialysis or continuous arteriovenous hemofiltration. A 3-day-old newborn with digoxin overdose and acute renal failure was treated with digoxin immune Fab and peritoneal dialysis. Low levels of total digoxin were measured in the dialyzate, indicating poor elimination of the digoxin-Fab complex through peritoneal dialysis.

Caffeine Overdose in an Adolescent Male

A 16 year old male who ingested an estimated 6-8 grams of caffeine is described. Caffeine is commonly thought to be harmless, but its wide availability has promoted abuse. This patient manifested many of the adverse effects seen in acute caffeine ingestion including hypokalemia, elevated blood glucose, tachycardia, bigeminy and agitation. Respiratory alkalosis and chest pain, which have not been previously reported to our knowledge in caffeine overdose, were also noted in this patient. Three serum caffeine levels were analyzed and an abnormally long elimination half-life of approximately 16 hours was calculated from the results.

Gastrointestinal Decontamination for Enteric-Coated Aspirin Overdose: What to Do Depends on Who You Ask

Context: Overdoses with enteric-coated preparation are common. The optimal means by which to limit drug absorption in such cases is controversial.Objective: To describe the recommendations for gastrointestinal decontamination issued by North American poison control centers for a hypothetical patient, (an adult male with normal vital signs), presenting 1 hour after ingesting 500 mg/kg of enteric-coated aspirin.Design: Telephone survey of 76 poison control centers in North America. Seven toxicologists who contributed to the American Academy of Clinical Toxicology/European Association of Poison Centres and Clinical Toxicologists position statements on gastrointestinal decontamination were also surveyed for informal comparison. Results: Most poison control centers (99%)and all of the toxicologists (100%) participated in the survey. Four centers (5%) recommended syrup of ipecac and 38 (51%) recommended gastric lavage, compared with 0% and 0% of toxicologists, respectively. Seventy-three centers (97%) recommended at least one dose of activated charcoal, compared with 6 toxicologists (86%). Twenty-one poison centers (28%) recommended whole-bowel irrigation, compared with 3 toxicologists (43%). A total of 36 different courses of action were suggested by respondents at the poison centers. Some of these recommendations were potentially harmful.Conclusions: Considerable variability exists in the recommendations of North American poison control centers for the gastrointestinal decontamination of patients with large, acute overdoses of enteric-coated aspirin.

An Unusual Skin Exposure to Copper; Clinical and Pharmacokinetic Evaluation

Skin exposure to copper is rare and has been described only with copper sulfate. A case of skin exposure to copper after an explosion of copper azide is presented. The amount of copper absorbed by this route was estimated to be 7.7 mg. Calculated distribution volume was 2.02 I/kg, half-life was 167.4 days and clearance was 0.0058 ml/min/kg. The authors also demonstrated metallic copper to be radiopaque, in contrast to copper salts. It is suggested that copper may be absorbed from the skin even if it is in the metal form. Careful clinical follow up as well as serial determinations of serum copper should guide the need for chelation therapy.

Activated charcoal in the home

Abstract The home use of activated charcoal (AC) has been proposed and studied since 1987. The availability of activated charcoal in the home provides the potential for earlier administration of AC and improved prevention of toxin absorption into the body. Review of the published data shows clear support for the claim that havign parents administer AC reduces the time delay associated with AC administration in an emergency department. These same reports show conflicting results regarding the success with which parents are able to administer the AC in the correct amount. None of the studies shed any light on the indications or contraindications for the home use of AC, none show clear improvements in patient outcome, and none characterize the clinical risks of such an intervention. The home use of AC is intuitively appealing, but more information is needed before the appropriateness of its widespread use can be judged.