Matjaz Bunc

The frequency of adverse drug reaction related admissions according to method of detection, admission urgency and medical department specialty

BackgroundAdverse Drug Reactions (ADRs) have been regarded as a major public health problem since they represent a sizable percentage of admissions. Unfortunately, there is a wide variation of ADR related admissions among different studies. The aim of this study was to evaluate the frequency of ADR related admissions and its dependency on reporting and method of detection, urgency of admissions and included medical departments reflecting department/hospital type within one study.MethodsThe study team of internal medicine specialists retrospectively reviewed 520 randomly selected medical records (3%) of patients treated in the medical departments of the primary city and tertiary referral governmental hospital for certain ADRs causing admissions regarding WHO causality criteria. All medical records were checked for whether the treating physicians recognised and documented ADRs causing admissions. The hospital information system was checked to ensure ADR related diagnoses were properly coded and the database of a national spontaneous reporting system was searched for patients with ADRs included in this study.ResultsThe established frequency of admissions due to certain ADRs recognised by the study team and documented in medical records by the treating physicians was the same and represented 5.8% of all patients (30/520). The frequency of ADR causing admissions detected by employing a computer-assisted approach using an ICD-10 coding system was 0.2% (1/520), and no patient admitted due to ADRs was reported to the national reporting system (0/520). The recognized frequency of ADR related admissions also depends on the departments specialty (p = 0.001) and acceptance of urgently admitted patients (p = 0.001). Patients admitted due to ADRs were significantly older compared to patients without ADRs (p = 0.025). Gastrointestinal bleeding due to NSAID, acetylsalicylic acid and warfarin was the most common ADR that resulted in admission and represented 40% of all certain ADRs (12/30) according to WHO causality criteria.ConclusionADRs cause 5.8% of admissions in medical departments in the primary city and tertiary referral hospital. The physicians recognise certain ADR related admissions according to WHO causality criteria and note them in medical records, but they rarely code and report ADRs. The established frequency of ADR related admissions depends on the detection method, department specialty and frequency of urgently admitted patients.

Polydipsia as another mechanism of hyponatremia after 'ecstasy' (3,4 methyldioxymethamphetamine) ingestion.

Acute symptomatic hyponatremia after ecstasy (3,4 methyldioxymethamphetamine; MDMA) ingestion is well documented and has been attributed to the syndrome of inappropriate antidiuretic hormone (SIADH). We report the case of an 18-year-old woman who took five tablets of ecstasy in a suicide attempt and drank 1700 ml water at the Emergency Department (ED). The laboratory findings obtained 5 h after ingestion showed a serum sodium concentration of 130 mmol/l, plasma osmolality of 264 mOsm/kg, urinary osmolality of 335 mOsm/kg and natriuresis of 101 mmol/l. The plasma arginine vasopressin level by radioimmunoassay was 33.7 pmol/l 5 h after ingestion. A gas chromatography-mass spectrometry assay confirmed MDMA in blood samples, with serum concentrations of 0.87 mg/l on arrival. This case report strongly suggests that MDMA reduces serum sodium levels through the dual pathways of SIADH and polydipsia. Accordingly, we believe that hyponatremia may be prevented in ED patients after MDMA ingestion by the early restriction of water intake.

Poisoning with 1-propanol and 2-propanol.

1-Propanol and 2-propanol are isomers of an alcohol with three carbons. They are colorless liquids with a sweet odor. 1-Propanol is metabolized by alcohol dehydrogenase to propionic acid and presents with metabolic acidosis and elevated anion gap, whereas 2-propanol is metabolized by alcohol dehydrogenase to acetone and presents with rapidly developing (within 3–4 h after exposure) ketosis and ketonuria but without metabolic acidosis. We report a patient who simultaneously ingested a lethal dose of 1-propanol and 2-propanol as a hand disinfectant in hospital. The patient lost consciousness and stopped breathing within half an hour after ingestion. He was intubated and artificially ventilated. Initial laboratory results showed mixed acidosis with elevated anion gap, but ketonuria appeared only 12 h after admission and 6 h following the regaining of consciousness. Therefore, laboratory results in simultaneous poisoning with two isomers of alcohol are not just a sum of laboratory results obtained in isolated poisoning with each isomer because they influence each other’s metabolism: 1-propanol retards the metabolism of 2-propanol to acetone. In conclusion, 1-propanol and 2-propanol poisoning presents early with mixed acidosis and elevated anion gap and only later with ketonuria.

Prolonged hypoglycaemia after insulin lispro overdose.

Insulin lispro has a more rapid onset and a shorter duration of hypoglycaemic action than regular insulin. We report a 39-year-old woman, with no previous medical history, who injected 300 U of the insulin lispro (Humalog) in an attempted suicide. Half an hour later, she was found comatose and brought to our emergency department. On arrival, she was comatose, with capillary glucose of 0.4 mmol/L. She awoke after a 50 ml intravenous bolus of 50% glucose. A continuous infusion of 10% glucose was started. Intermittent hypoglycaemia with neurological signs requiring treatment with 50% glucose was recorded three times during subsequent hospitalization, the last episode being 11 h after insulin injection. The plasma insulin level 4 h after injection was 1465 mU/L, and 18 h after injection was 11 mU/L. Hypoglycaemia after an insulin lispro overdose may last for more than 11 h. Repeated hypoglycaemia after an insulin overdose could be avoided with a glucose infusion rate equivalent to the maximal glucose disposal rate.

S100B protein in conscious carbon monoxide-poisoned rats treated with normobaric or hyperbaric oxygen.

Objective:To evaluate S100B, an astroglial structural protein, during normobaric and hyperbaric oxygen therapy of conscious carbon monoxide (CO)-poisoned rats. So far, the usefulness of hyperbaric oxygen therapy in conscious CO-poisoned patients has been shown with neuropsychological testing. The S100B protein has been demonstrated as a possible biochemical marker and prognostic parameter in CO-poisoned rats. Design:Randomized, controlled interventional trial. Setting:University laboratory. Subjects:Male Wistar rats weighing 254 ± 14 g. Interventions:The rats were exposed to a mixture of 3,000 ppm CO in air for 60 mins. After CO exposure, the first group of eight conscious rats was exposed to ambient air for 30 mins, the second group of six conscious rats was exposed to 100% normobaric oxygen for 30 mins, and the third group of six conscious rats was exposed to 100% hyperbaric oxygen at 3 bars for 30 mins. Blood samples were taken from the jugular vein just before CO exposure and immediately after oxygen therapy. The level of consciousness was evaluated at the end of exposure, and the survival rate was monitored for 14 days. The S100B concentrations were measured with a commercial immunoluminometric assay. Measurements and Main Results:Analyses of differences in S100B levels between different kinds of therapy before and after treatment showed a global significant difference (p = .002). The post hoc test results showed that S100B levels after therapy of the first group treated with ambient air (0.16 ± 0.07 &mgr;g/L) and the second group treated with normobaric oxygen (0.19 ± 0.05 &mgr;g/L) were similar (p = .741), and both of them were significantly different, with much higher values of S100B levels after therapy, from the third group treated with hyperbaric oxygen (0.06 ± 0.03 &mgr;g/L; p = .018 and p = .002, respectively). All the rats survived. Conclusions:S100B is elevated in conscious CO-poisoned rats left on ambient air or treated with normobaric oxygen, but not in conscious CO-poisoned rats treated with hyperbaric oxygen.

Metabolic acidosis in prometryn (triazine herbicide) self-poisoning.

Introduction. Prometryn is a triazine herbicide, which is one of the most extensively used groups of herbicides. The mechanism of acute triazine herbicide toxicity in humans is not known. We report a first case of acute prometryn poisoning. Case report. A 62-year-old male ingested 50 g of prometryn and ethanol in a suicide attempt. On arrival two hours after ingestion, he was somnolent and vomited. Seven hours after ingestion laboratory tests showed metabolic acidosis with a calculated anion gap of 47.5 mmol/L and lactate of 23.4 mmol/L. Gas chromatography/mass spectrometry revealed serum prometryn concentrations of 48.1 mg/L. Hemodialysis corrected metabolic acidosis, but the serum prometryn concentration increased to 67.7 mg/L. The lactate level after hemodialysis was 11.7 mmol/L and returned within normal limits 47 hours after ingestion. The patient was discharged without any sequelae after psychiatric evaluation. Conclusion. In high anion gap metabolic acidosis we should consider poisoning with prometryn and other triazine herbicides. Hemodialysis corrects metabolic derangements, but it does not lower serum prometryn concentration.

Butanol ingestion in an airport hangar

1–Butanol is a colourless organic solvent with a rancid sweet odour. 1–Butanol ingestion may result in vomiting, abdominal pain, headache, drowsiness and unconsciousness. We present a 47–year–old male with no previous medical history, who was found comatose and soiled after having vomited while unconscious. On arrival, he had a Glasgow coma scale of 3, tachycardia, hypotension, shallow tachypnoic breathing, hypotonic muscles, absent myotatic reflexes and aromatic odour. The patient was intubated and treated with oxygen, dopamine and volume replacement therapy. Gastric lavage was performed and activated charcoal was given. His initial laboratory test revealed hypokaliemia, renal failure, acidosis with elevated lactate and hypercapnic respiratory insufficiency. Twelve hours after admission, the patient started to respond to a painful stimulus and 4 h later he was conscious. He was extubated 23 h after admission. All pathological laboratory results gradually returned within normal limits. The subsequent toxicological examination of gastric content and urine sample by gas chromatography revealed 1–butanol. On awakening, he confirmed ingestion of a solvent stored in an airport hangar. In conclusion, we describe a patient who ingested an unknown dose of 1–butanol. Symptoms were headache, vomiting, abdominal pain, coma, muscular hypotonus, hypotension, respiratory insufficiency and mixed acidosis. The patient totally recovered after supportive therapy over 30 h. In future cases, intravenous administration of ethanol or even hemodialysis can be considered analogous to the treatment of methanol and ethylene glycol poisoning.

Recording of ENGs from the nerves innervating the pancreas of a dog during the intravenous glucose tolerance test

Electroneurograms (ENGs) from the vagus nerve (VN), the splanchnic nerve (SN) and the pancreatic nerve (PN) innervating the pancreas of a dog, were recorded with chronically implanted 33-electrode spiral cuffs (cuff) before and after the pancreas were stimulated with intravenously (i.v.) administered glucose. In the cuffs platinum electrodes were arranged in three parallel spiral groups containing 11 electrodes on the inner surface. The cuffs had an inner diameter of 2 mm and a length of 18 mm. In a two-year study, the cuffs were implanted into two Beagle dogs and were also used for pancreatic stimulation, although this is not described in this paper. In the VN, the cuff was installed on the nerve at the neck, whilst in the SN, the cuff was installed on the nerve before the celiac ganglion, and in the PN, the cuff was installed on the nerve just before it enters the pancreas. Six months after implantation, when the model of interpretation of the results was developed, three recordings of ENG in each animal were conducted. The first one was conducted in the unstimulated pancreas while the second and the third were conducted 1 and 8 min after a known amount of glucose was i.v. administered. Since the results obtained in both animals were actually quite similar, we present the results obtained in one animal. To evaluate the changes in superficial activity of the nerves, elicited by the administration of glucose, the power spectra corresponding to ENGs, recorded from the nerves before and after the administration of glucose, were integrated within the band of frequencies ranging from 1 to 5 kHz. Accordingly, the magnitude of the integrated power spectrum (MIPS), corresponding to the ENG recorded from the SN before administration of glucose, was 2.863 au. One minute after glucose was administered the value fell to 2.795 au while 8 min after the administration the value returned to 2.8 au. The MIPS corresponding to the ENG recorded from the PN before the administration of glucose was 3.236 au. One minute after the administration the value fell to 2.901 au while 8 min after the administration the value rose to 3.009 au. The MIPS, corresponding to the ENG recorded from the VN before the administration of glucose, was 3.656 au. One minute after the administration the value fell to 3.565 au. Eight minutes after the administration the value rose to 3.689 au. The results show that 1 min after glucose was administered superficial activity in all three nerves was reduced while 8 min after administration the activity in the nerves returned to the same level of activity before the glucose was administered. This information could be effectively used in a further study of pancreatic innervation and its function. Moreover, the results suggest that cuffs could also be useful in recording the ENGs from other nerves of the autonomic nervous system that innervate various glands and internal organs.

Trimetazidine shortens QTc interval in patients with ischemic heart failure.

Background: Trimetazidine improves functional class and left ventricular function in patients with heart failure; however, its potential impact on QTc interval remains undefined. We analyzed the effects of trimetazidine on QTc interval in patients with ischemic heart failure. Methods: A prospective trial included 42 patients with ischemic heart failure (New York Heart Association [NYHA] 2 or 3) and reduced left ventricular ejection fraction (<55%), who were randomly allocated to conventional therapy plus trimetazidine in a modulated release formulation (35 mg twice daily; 22 patients) or conventional therapy alone (20 patients; controls). We measured QTc interval at baseline and after 1 month. Results: At baseline, QTc interval duration was similar in both groups (443 ± 41 milliseconds in trimetazidine group vs 446 ± 27 milliseconds in controls, P = .62). After 1 month, QTc interval decreased in the trimetazidine group (404 ± 36 milliseconds, P = .0002) but not in controls (452 ± 25 milliseconds, P = .74). QTc interval shortening with trimetazidine was more pronounced in patients with prolonged (>440 milliseconds) baseline QTc interval (—45 ± 38 milliseconds) than in patients with normal QTc interval (—19 ± 19 milliseconds P = .04). Significant QTc interval shortening (>20 milliseconds) was present in 14 of 22 patients (64%) in trimetazidine group compared to 3 of 20 (15%) patients in control group (P = .002). Conclusions: Trimetazidine therapy is associated with QTc interval shortening in patients with ischemic heart failure.

Urinary serotonin level is associated with serotonin syndrome after moclobemide, sertraline, and citalopram overdose

Introduction. Altered mental status, autonomic dysfunction, and neuromuscular abnormalities are a characteristic triad of serotonin syndrome. No laboratory tests confirm the diagnosis of serotonin syndrome. Case report. A 35-year-old woman took moclobemide, sertraline, and citalopram in a suicide attempt. She was conscious with mild tachycardia, hypertension, and tachypnea one hour after ingestion. In the second hour after ingestion diaphoresis, mydriasis, horizontal nystagmus, trismus, hyperreflexia, clonus, and tremor appeared. She became agitated and unresponsive. In the third hour after ingestion she became comatose and hyperthermic. She was anesthetized, paralyzed, intubated, and ventilated for 24 hours. Serum moclobemide, sertraline, and citalopram levels were above therapeutic levels. The serum serotonin level was within normal limits and the urinary 5-hydroxyindoleacetic acid:creatinine ratio was below the average daily value. The urinary serotonin:creatinine ratio was increased on arrival (1 mg/g). Discussion and conclusion. The urinary serotonin level is increased in serotonin syndrome due to a monoamine oxidase inhibitor and selective serotonin-reuptake inhibitors overdose. It is possible that urinary serotonin concentration could be used as a biochemical marker of serotonin syndrome.