Dag Jacobsen

Ethylene glycol intoxication: Evaluation of kinetics and crystalluria

Ethylene glycol and glycolate kinetics were studied in two cases of ethylene glycol intoxication with maximal ethylene glycol/glycolate concentrations of 40.9/26.8 and 56.4/22.4 mmol/liter, respectively. Both patients survived, but with prolonged renal failure, upon treatment with bicarbonate, ethanol, and hemodialysis. Glycolic acid was the major cause of the metabolic acidosis in both cases; lactate levels were only slightly elevated. Kinetic calculations showed that both ethylene glycol and glycolate were distributed in total body water with plasma half-lives of 8.4 and 7.0 hours, respectively. The half-life of ethylene glycol was increased more than 10-fold by ethanol treatment alone. Calcium oxalate monohydrate crystalluria was dominant in both cases, but in one was preceded by a short period with mainly dihydrate excretion; crystalluria was not present upon admission. Repetitive urine microscopy in search of needle- or envelope-shaped crystals should be performed when ethylene glycol intoxication is suspected.

Methanol outbreak in Norway 2002-2004: epidemiology, clinical features and prognostic signs

Objectives.  Knowledge on methanol poisoning does mainly come from clinical studies. We therefore report epidemiological, clinical and prognostic features from the large methanol outbreak in Norway in 2002–2004 where the new antidote fomepizole was the primary antidote in use.

Strong and weak aspects of an established post-resuscitation treatment protocol—A five-year observational study

AIM OF STUDY Favourable hospital survival increased from 26% to 56% in the implementation phase of a new standard operating procedure (SOP) for treatment after out-of hospital cardiac arrest (OHCA) in 2003. We now evaluate protocol adherence and survival rates after five years with this established SOP. METHODS This observational study is based on prospectively collected registry data from all OHCA patients with cardiac aetiology admitted with spontaneous circulation to Ulleval Hospital between September 2003 and January 2009. Three patient categories are described based on early assessment in the emergency department: conscious, comatose, and comatose patients receiving only palliative care, with main focus on comatose patients receiving active treatment. RESULTS Of 248 patients, 22% were consciousness on admission, 70% were comatose and received active treatment, while 8% received only palliative care. Favourable survival from admittance to discharge remained at 56% throughout the study period. Among actively treated patients 83% received emergency coronary angiography and 48% underwent subsequent percutaneous coronary intervention. In this cohort 63% had an acute myocardial infarction, ten of whom did not receive emergency coronary angiography. Among actively treated comatose patients, 6% survived with unfavourable neurology, while 51% of the deaths followed treatment withdrawal after prognostication of severe brain injury. CONCLUSION The previously reported doubling in survival rate remained throughout a five-year study period. Establishing reliable indication for emergency coronary angiography and interventions and validating prognostication rules in the hypothermia era are important challenges for future studies.

Adverse events after naloxone treatment of episodes of suspected acute opioid overdose.

Objective: An increasing and serious heroin overdose problem in Oslo has mandated the increasing out-of-hospital use of naloxone administered by paramedics. The aim of this study was to determine the frequencies and characteristics of adverse events related to this out-of-hospital administration by paramedics. Methods: A one-year prospective observational study from February 1998 to January 1999 was performed in patients suspected to be acutely overdosed by an opioid. A total of 1192 episodes treated with naloxone administered by the Emergency Medical Service system in Oslo, were included. The main outcome variable was adverse events observed immediately after the administration of naloxone. Results: The mean age of patients included was 32.6 years, and 77% were men. Adverse events suspected to be related to naloxone treatment were reported in 45% of episodes. The most common adverse events were related to opioid withdrawal (33%) such as gastrointestinal disorders, aggressiveness, tachycardia, shivering, sweating and tremor. Cases of confusion/restlessness (32%) might be related either to opioid withdrawal or to the effect of the heroin in combination with other drugs. Headache and seizures (25%) were probably related to hypoxia. Most events were non-serious. In three episodes (0.3%) the patients were hospitalized because of adverse events. Conclusion: Although adverse events were common among patients treated for opioid overdose in an out-of-hospital setting, serious complications were rare. Out-of-hospital naloxone treatment by paramedics seems to save several lives a year without a high risk of serious complications.

Methanol mass poisoning in Estonia: Outbreak in 154 patients

Background. Knowledge of methanol toxicity is based on human data from case series and larger outbreaks. In many of these cases, however, diagnosis was not verified by methanol determinations. We present epidemiological and clinical data from one of the largest methanol outbreaks in which all patients had detectable serum methanol levels. Methods. Retrospective case series study of hospital and forensic charts from the five hospitals where patients were treated. Results. Of the 147 patients admitted with suspected methanol poisoning, the diagnosis was confirmed in 111, of whom 25 (23 %) died. In addition, 43 patients died outside the hospital, giving a total of 154 patients and a death toll of 68 (44 %). Outcome was related to the degree of metabolic acidosis, serum methanol concentration, coma upon admission, and the patients ability to hyperventilate. Patients were treated with bicarbonate (85 %), ethanol (87 %), hemodialysis (71 %), and mechanical ventilation (61%) according to clinical features and blood gases, since serum methanol concentrations were analyzed retrospectively. Twenty patients (18 %) survived with permanent sequelae, 18 suffered from impaired vision, and 3 developed permanent brain damage. Discussion. Given limited resources, triage and use age of tertiary care centers allowed a small community hospital to treat a high number of methanol-poisoned patients. Critical resources were ventilators and dialyzing machines, whereas stores of antidote (ethanol) and bicarbonate were sufficient. Many patients were mechanically ventilated by hand and treated with bicarbonate and ethanol during transport to tertiary care centers for hemodialysis.

Anion and osmolal gaps in the diagnosis of methanol poisoning: clinical study in 28 patients

Objective To evaluate anion and osmolal gaps as diagnostic tools in methanol poisoning.Design and setting Clinical observational study.Patients and methods In a recent methanol outbreak, the initial triage and treatment decisions in 28 patients were based mainly upon the values of the osmolal and anion gaps on admission. Methanol and formate levels were later compared to these gaps by linear regression analysis.Results The correlation between the osmolal gaps and serum methanol concentrations on admission was linear (y = 1.03x+12.71, R2 = 0.94). The anion gaps correlated well with the serum formate concentrations (y = 1.12x+13.82, R2 = 0.86). Both gaps were elevated in 24 of the 28 subjects upon admission. Three patients had an osmolal gap within the reference area (because of low serum methanol), but elevated anion gap because of formate accumulation. One patient with probable concomitant ethanol ingestion had a high osmolal gap and a normal anion gap.Conclusion Osmolal and anion gaps are useful in the diagnosis and triage of methanol-exposed subjects. Confounders are low serum methanol and concomitant ethanol ingestion.

Morphine-6-Glucuronide might Mediate the Prolonged Opioid Effect of Morphine in Acute Renal Failure

1 A 43-year-old male developed acute kidney failure due to ethylene glycol poisoning. He was treated with bicarbonate to combat metabolic acidosis, ethanol as an antimetabolite and haemodialysis to remove the glycol and its toxic metabolites. He was kept on a respirator and sedated with morphine. Peritoneal dialysis was given for 36 d. Following sedation with morphine for 11 d, the patient was given naloxone and then extubated. The antidote had to be continued for 14 d to prevent respiratory depression, until kidney function improved. 2 Only morphine-6-glucuronide (M-6-G) was found in the plasma and CSF at concentrations which might explain the opioid effects observed in the patient during the days after the cessation of morphine treatment. The ratio of the area under the concentration-time curve (AUC) of morphine-3-glucuronide (M-3-G) to M-6-G was 2:1. The elimination half-lives of M-3-G and M-6-G were 55 and 82 h, respectively. The clearance data indicate that most of the glucuronides were eliminated by peritoneal dialysis during renal failure. 3 The data suggest that M-6-G exerts opioid effects and is retained in acute kidney failure. Morphine should therefore not be used preferentially as a sedative/analgesic in pronounced kidney failure.

Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans

4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, may be useful for the treatment of methanol and ethylene glycol intoxications. A placebo-controlled, double blind, multiple dose, sequential, ascending-dose study has been performed to determine the tolerance of 4-MP in healthy volunteers. Oral loading doses of 4-MP were followed by supplemental doses every 12 h through 5 days, producing plasma levels in the therapeutic range. A slight, transient elevation in one or both serum transaminase values was observed in 6 of the 15 subjects treated with 4-MP. This effect was not dose related nor apparently mediated through a hypersensitivity reaction. Serum triglyceride levels were increased in 30% of 4-MP treated subjects, but also in 25% of the placebo subjects. 4-MP treatment did not produce any other significant changes in objective clinical parameters nor in subjective side effects. The results suggest that a mild, transient increase in liver function tests might be observed in some subjects treated with multiple doses of 4-MP. Nevertheless, the slower elimination rate and lesser degree of toxicity of 4-MP would make it preferable to ethanol in therapy of these poisonings.

Methanol poisoning and long term sequelae – a six years follow-up after a large methanol outbreak

BackgroundMass poisonings with methanol are rare but occur regularly both in developed and in developing countries. Data from the poisoning episodes are often published, but follow-up-data is scarce. We therefore conducted a six year follow-up study after the large methanol outbreak in Estonia in September 2001.MethodsSurviving victims from the outbreak were contacted and invited to an interview and a clinical evaluation by an ophthalmologist and a physician. The patients that failed to respond were searched for in the Estonian Register of Population and through their General Practitioner.ResultsDuring the outbreak in 2001, 86/111 hospitalized patients survived: 66 without sequelae (Group I) and 20 with sequelae (Group II). Six years later, 26/86 were dead, 33/86 could not be tracked down, and so only 27/86 of these were followed up and examined: 22/66 of the patients in Group I, and 5/20 in Group II were found and examined. From Group I, 8/22 were identified with new neurological impairment and 8/22 with new visual disturbances after discharge. From Group II, visual disturbances (n = 4) and neurological impairment (n = 3) were still present in all patients. Among the 26 dead, 19 were from Group I, and seven were from Group II. Alcohol intoxication was the most frequent cause of death (7/26).ConclusionAll sequelae were still present six years after the initial poisoning suggesting that these were irreversible damages. On follow-up, apparently new neurological and visual complications were identified in 36% and 36%, respectively. 35% of the patients initially discharged with sequelae and 29% discharged without were dead six years later; 27% of them from alcohol intoxication.

Acute poisonings treated in hospitals in Oslo : A one-year prospective study (I): Pattern of poisoning

Objectives. Prospective design is mandatory to study pattern of poisoning and suicidal intention of patients. Material and Methods. Prospective cross-sectional multi-center study of all patients contacting health care services because of acute poisoning during one year in Oslo, irrespective of intention. Data on the adult hospitalized patients (≥16 years) are presented here. Results. Of a total of 3,775 such adult contacts (3,025 episodes), there were 947 (31 %) hospitalizations; annual incidence 1.9 (per 1,000) in males and 2.1 in females. Median age was 36 years (range 16–89); 54% females. Benzodiazepines (18%), ethanol (17%), paracetamol (12%), opioids (7%), and gamma hydroxybutyric acid (GHB) (7%) were most frequently taken. Patients stated suicidal intention in 29% of the admissions; physicians in 10%. Conclusion. Benzodiazepines and ethanol were the most common agents, but newer illicit drugs were frequent, especially GHB. Males often took ethanol and drugs of abuse; females often used prescription drugs with suicidal intention.