Pierre Gaudreault

Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation.

ObjectivesTo summarize and compare different prognostic criteria used to determine need for liver transplantation in patients with fulminant hepatic failure secondary to acetaminophen poisoning. Data SourcesStudies published in the literature that investigated criteria for hepatic transplantation secondary to acetaminophen-induced liver failure as identified by a preestablished MEDLINE strategy (1966 through October 2001). Study SelectionStudies were included if 2 × 2 tables could be reconstructed and if they did not assume that patients undergoing transplantation would have eventually died had they not received the transplant. Data ExtractionRelevant articles were reviewed by two authors independently. Discrepancies or disagreements, if any, on the inclusion or exclusion of studies were resolved by consulting the third author. Data SynthesisKing’s criteria (pH < 7.30 or prothrombin time of >100 secs plus creatinine of >300 &mgr;mol/L plus encephalopathy grade of ≥3) were evaluated in nine studies, pH < 7.30 in four, prothrombin time of >100 secs in three, prothrombin time of >100 secs plus creatinine of >300 &mgr;mol/L plus encephalopathy grade of ≥3 in three, creatinine of >300 &mgr;mol/L in two, and one each for increase in prothrombin time day 4, factor V of <10%, Acute Physiology and Chronic Health Evaluation (APACHE) II score of >15, and Gc-globulin of <100 mg/L. King’s criteria were more sensitive than pH: 69% (95% confidence interval, 63–75) vs. 57% (95% confidence interval, 44–68). Their specificities were, however, comparable: 92% (95% confidence interval, 81–97) vs. 89% (95% confidence interval, 62–97). APACHE II score of >15 had the highest positive likelihood ratio (16.4) and the lowest negative likelihood ratio (0.19) but was evaluated in only one study. The accuracy measures of all other criteria were lower than that of King’s criteria or pH < 7.30. ConclusionsPresently, available criteria are not very sensitive and may miss patients requiring transplantation. Future studies should further evaluate the efficacy of the APACHE II criteria.

Theophylline poisoning. Pharmacological considerations and clinical management.

SummaryThe recent marketing of slow release preparations of theophylline and new indications for the use of the drug have resulted in a marked increase in the sale of theophylline products. This phenomenon combined with the drug’s highly variable pharmacokinetics has led to an increase in the number of theophylline intoxications.The morbidity and mortality rates associated with theophylline intoxication are significant. Therefore it is essential that clinicians are aware of the pathophysiology, clinical presentation and treatment of this poisoning. Theophylline intoxication mainly affects the gastrointestinal, cardiovascular and central nervous systems. Signs and symptoms range from mild gastrointestinal upset to serious central nervous system manifestations such as seizures, a symptom often associated with a bad prognosis.Theophylline serum concentrations are very useful for making decisions regarding treatment. However, their interpretation should take into account several factors such as the age of the patient and the type of intoxication (acute versus chronic).Prevention of gastrointestinal absorption should be the principal objective of treatment of an oral theophylline poisoning. The repetitive administration of activated charcoal not only prevents theophylline absorption but also increases its rate of elimination. Once absorbed, external methods such as haemodialysis and haemoperfusion can significantly accelerate the elimination of the drug from the body. Finally, the rapid suppression of seizures and cardiac arrhythmias are essential to prevent severe neurological sequelae and death.Since theophylline intoxication can be potentially life-threatening, its administration should be monitored with regular measurements of the serum theophylline concentration, especially in the very young and the very old.

Pharmacokinetics and clinical efficacy of intrarectal solution of acetaminophen

Acetaminophen is frequently administered orally to children for its analgesic properties, although its potency has never been clearly evaluated in this population. In certain situations (patients vomiting or unconscious), acetaminophen has to be given rectally. However, the rectal absorption of suppositories is frequently erratic. We undertook this study first, to measure the absorption of an aqueous solution of acetaminophen administered rectally. Secondly, we evaluated acetaminophen’s postoperative analgesic effects in children aged 1 to 8 years old undergoing adenoidectomy and/or tonsillectomy and compared its efficacy to meperidine. Twenty children received 20 mg·kg-1 of acetaminophen at the time of induction of anaesthesia while 20 others received 1 mg·kg-1 of meperidine intramuscularly. Thirty-two patients required meperidine in the Recovery Room. There was no statistical difference between the patients who received acetaminophen (18), and those who received meperidine (14). The absorption of acetaminophen was incomplete (peak serum concentration: 70.8 µnol·L1) and delayed. We conclude that the rectal administration of acetaminophen at the induction of anesthesia results in incomplete and delayed absorption and does not prevent the occurrence of immediate postoperative pain in children undergoing adeno-tonsillectomy.RésuméĽacétaminophène est un médicament fréquemment utilisé en pédiatrie pour ses propriétés analgésiques quoique son efficacité n’est pas été bien étudié dans cette population. Dans certaines situations cliniques, telles les vomissements et ľinconscience, les médicaments doivent être administrés par voie rectale. Toutefois il est bien connnu que ľabsorption des suppositoires est souvent erratique. C’est pourquoi nous avons étudié ľabsorption rectale ďune solution aqueuse ďacétaminophène. De plus, nous avons comparé son effet analgésique à celui de la mépéridine chez 40 enfants agés de un à huit ans admis pour adéno-amygdalectomie. Au moment de ľinduction anesthésique, 20 patients ont reçu 20 mg·kg-1 ďacétaminophène intrarectal alors que les autres ont reçu 1 mg·kg1 de mépéridine intra-musculaire. čanalgésie post-opératoire s’est avérée insuffisante chez 32 patients (acétaminophène: 18, mépéridine: 14). čabsorption de ľacétaminophène a été incomplète (concentration sérique maximale: 70.8 µmol·L1) et retardée. En conclusion, ľadministration intra-rectale ďacétaminophène au moment de ľinduction anesthésique ne procure pas une analgésie post-opératoire adéquate et entraine une absorption incomplète et retardée.

Benzodiazepine poisoning. Clinical and pharmacological considerations and treatment.

SummaryBenzodiazepines are among the most frequently prescribed drugs worldwide. This popularity is based not only on their efficacy but also on their remarkable safety. Pure benzodiazepine overdoses usually induce a mild to moderate central nervous system depression; deep coma requiring assisted ventilation is rare, and should prompt a search for other toxic substances. The severity of the CNS depression is influenced by the dose, the age of the patient and his or her clinical status prior to the ingestion, and the coingestion of other CNS depressants. In severe overdoses, benzodiazepines can occasionally induce cardiovascular and pulmonary toxicity, but deaths resulting from pure benzodiazepine overdoses are rare.Quantitative determinations of benzodiazepines are not useful in the clinical management of intoxicated patients since there is no correlation between serum concentrations and pharmacological and toxicological effects.Benzodiazepine overdoses occurring during pregnancy rarely induce serious morbidity in mothers or fetuses, although large doses administered near delivery can induce respiratory depression in neonates. The teratogenic potential of benzodiazepines remains controversial, but is probably small if it exists at all.There is clear evidence that the prolonged use of even therapeutic doses of benzodiazepines will lead to dependence. The risk of developing significant withdrawal symptoms is related to dosage and duration of treatment.Prevention of gastrointestinal absorption should be initiated in all intentional benzodiazepine overdoses. Forced diuresis and dialysis techniques are not indicated since they will not significantly accelerate the elimination of these agents. Intravenous administration of flumazenil, a pure benzodiazepine antagonist, effectively reverses benzodiazepine-induced CNS depression.

Pharmacokinetics of sufentanil in normal children

The pharmacokinetic variables of sufentanil were studied in 20 healthy children between two and eight years of age. The plasma concentrations of sufentanil were measured for up to 480 min after administration of a bolus of sufentanil, 1–3 μg · kg−1. The distribution half-life (t1/2β) was 5.2 ±2.2 (mean ±SD) min and the elimination half life (t1/2β) was 97.0 ±42.0 min. The volume of distribution at steady state (Vdss) was 2.9 ±0.6 L · kg−1 and the clearance was 30.5 ±8.8 ml · kg−1 · min−1. The Vdss was one and a half limes greater than that reported in adults when expressed as a function of body weight but similar to that of adults when expressed as a function of body surface area. According to our results, the clearance of sufentanil in normal children between two and eight years of age is twice as rapid as that described in adults and adolescents. A greater clearance of sufentanit in children suggests that they would require relativelygreater maintenance doses than adults.RésuméLa pharmacocinétique du sufentanil a été étudiée chez 20 enfants agés de deux à huit ans. Les concentrations plasmatiques ont pu être mesurées jusqu ’à 480 min après l’administration d’un bolus de 1 à 3 μg · kg−1 de sufentanil. La demi-vie de distribution (t1/2α) était de 5.2 ±2,2 min et la demi-vie d’élimination (t1/2β) était de 97,0 ±42,0 min. Le volume de distribution à l’état d’équilibre (Vdss) était 2,9 ±0,6 L · kg−1 et la clairance 30,5 ±8,8 ml · kg−1 · min−1. Le Vdss est égal à environ une fois et demi celui de précédemment rapporté pour l’adulte lorsqu’il est exprimé en fonction du poids corporel et superposable à celui-ci lorsqu’il est exprimé en fonction de la surface corporelle. D’après nos résultats la clairance du sufentanil chez l’enfant normal de deux à huit ans est environ deux fois celle décrite chez l’adolescent et l’adulte. Une clairance augmentée suggère que les enfants nécessitent des doses d’entretien plus élevées.

Prevalence of potential risk factors in victims of electrocution

OBJECTIVE To identify risk factors of fatal arrhythmia following electrical shock, by comparing the prevalence of transthoracic current, tetany, decreased skin resistance because of wet extremities, skin burns and heart disease in victims of electrocution with instant as opposed to delayed death. DESIGN Retrospective case-control study, based on the charts from the coroners office. RESULTS A total of 124 deaths from electrocution occurred between 1987 and 1992. One victim presumably died from delayed arrhythmia and was excluded from the study. Twenty victims had decreased skin resistance because of wet extremities and five had tetany. Autopsy revealed coronary heart disease in 21 cases, and burns in 109; 10 did not have any skin lesion. There was no difference in risk factors between those who died instantly presumably from arrhythmia (n=114) and those who died later from other causes (n=9). CONCLUSION No differences in risk factors were found between victims who died immediately from arrhythmia following electrical shock and those died later from other causes.

Admission to a pediatric intensive care unit for poisoning: a review of 105 cases

We reviewed all patients treated for intoxication in the pediatric ICU (PICU) of the Sainte-Justine Hospital over a 3-yr period. Poisoning (105 patients) constituted 3.1% of PICU admissions. Most involved children less than 3 (42%) yr or greater than 12 (33%) yr. Products most commonly ingested included tricyclic antidepressants (22%), benzodiazepines (15%), theophylline (10%), ethanol (10%), hallucinogens (8%), salicylates (8%), narcotics (8%), antihistamines (7%), and carbamazepine (5%). Three children became comatose after ingesting about 1 g of hashish. Multiple drug ingestions were frequent (22%), particularly in suicide attempts (11/23). Treatment was, in general, interventionist and nonspecific; aggressive measures for poisoning were required in only two patients who were hemodialyzed. Two patients stayed in the PICU greater than 2 days. All patients survived with no sequelae, except for one patient who required an intestinal resection. Poisoning in children is a common occurrence leading to PICU admission; however, the medical prognosis is usually excellent.

Single daily doses of trimethoprim/sulphadiazine for three or 10 days in urinary tract infections

We conducted a prospective randomized study to evaluate the efficacy of a single daily dose of 4 mg/kg of trimethoprim coupled with 17.5 mg/kg of sulphadiazine for three (group 1) or 10 days (group 2) in the treatment of uncomplicated urinary tract infections in children. Forty patients (nine boys and 31 girls) aged 2.5‐18 years, presenting with a urinary tract infection were allocated to one of the two groups. Patients were seen three, 10, and 38 days after the initiation of treatment. Control urine cultures were negative in all patients at days 3 and 10. Two patients in group 1 and one patient in group 2 suffered a relapse within a month. Single doses of trimethoprim/sulphadiazine for three or 10 days are effective in the treatment of uncomplicated urinary tract infections in children.

Residual curarization in the neonate after Caesarean section

The transplacental transfer and the neonatal effects of atracurium 0.3 mg· kg−1(ED95) were compared with those of d-tubocurarine at the usual clinical dose of 0.3 mg · kg−1 (ED90) in 46 patients undergoing elective Caesarean section. The atracurium group (25 patients) was similar to the d-tubocurarine group (21 patients) as far as age, parity and time intervals between precurarization, induction, skin incision, muscle relaxant administration, hysterotomy and birth. The transplacental transfer of atracurium was lower than that of d-tubocurarine, with a feto-maternal ratio of 9 ± 3% for atracurium and 12 ± 5% for d-tubocurarine (P < 0.05). The transplacental transfer of laudanosine was low at 14 ± 5%, with blood levels of 0.101 ± 0.032 μM · L−1 in the umbilical vein. Newborns in the two groups were comparable in terms of Apgar scores at one, five and ten minutes, as well as for NACS scores (neurological and adaptive capacity scoring test) at two and 24 hours after birth. However, at 15 min after birth, only 55% of newborns in whom the mothers received atracurium had a normal NACS score (≥ 35/40) compared with 83% of newborns in whom the mothers received d-tubocurarine (P < 0.05). Further analysis of the five variables related to active muscle tone revealed that the modal score for active extension of the neck of newborns from the atracurium group was lower than for newborns from the d-tubocurarine group (P < 0.01). This was compatible with the effect of residual curarization among newborns in whom the mothers received atracurium. However, this effect was transient since there was no difference found between the two groups at two and 24 hr after birth. Furthermore, no newborn had clinical signs of respiratory distress. In conclusion, atracurium given at a dose of 0.3 mg · kg−1 for Caesarean section may lead to partial residual curarization of neonates 15 min after birth.RésuméLe passage transplacentaire et les ejfets sur le nouveau-né de l’atracurium à 0.3 mg · kg−1 (ED95) ont été comparés a ceux de la d-tubocurarine à dose clinique habituelle de 0.3 mg · kg−1 (ED90) chez 46 patientes devant subir une césarienne élective. Le groupe atracurium (25 patientes) était semblable à celui de la d-tubocurarine (21 patientes) concernant l’âge, la parité et les intervalles entre la précurarisation, l’induction, l’incision cutanée, l’administration du myorésolutif, l’hystérotomie et la naissance. Le passage transplacentaire de l’atracurium était légèrement inférieur à celui de la d-tubocurarine, avec un rapport foeto-maternel de 9 ± 3% pour l’atracurium et de 12 ± 5% pour la d-tubocurarine (P < 0.05). Le passage transplacentaire de la laudanosine était faible avec un rapport de 14 ± 5% et des niveaux sériques de 0.101 ± 0,032 μM · L−1 dans la veine ombilicale. Les nouveau-nés des deux groupes étaient comparables pour l’Apgar à une, cinq et dix minutes ainsi que pour le NACS (“neurological and adaptive capacity scoring test”) à deux heures et 24 heures de vie. Cependant, à 15 min de vie, seulement 55% des nouveau-nés dont les mères avaient reçu de l’atracurium avaient un pointage normal pour le NACS (≥35/40) par rapport à 83% des nouveau-nés dont les mères avaient reçu de la d-tubocurarine (P < 0,05). Une analyse plus détaillée des cinq variables évaluant le tonus musculaire actif a démontré que la valeur modale pour l’extension active du cou était moins élevée chez les nouveau-nes du groupe atracurium que chez ceux du groupe d-tubocurarine (P < 0.01). Ceci est compatible avec une curarisation résiduelle chez les nouveaunés dont les mères ont reçu de l’atracurium. Cependant, cet effet était transitoire puisqu’il n’y avail plus aucune difference entre les deux groupes à deux et 24 heures de vie. De plus, aucun nouveau-né n’a eu de signes cliniques de détresse respiratoire. Nous concluons que l’atracurium administrée à une dose de 0.3 mg·kg−1 tors d’une césarienne peut causer une curarisation résiduelle partielle chez le nouveau-né à 15 minutes de vie.

Lidocaine hydrocarbonate and lidocaine hydrochloride for cesarean section: transplacental passage and neonatal effects

Twenty‐six patients, ASA physical status 1, scheduled for elective cesarean section, were divided at random into two groups and received via an epidural catheter 20 ml of 2.2% lidocaine hydrocarbonate (17.3 mg · ml‐1 lidocaine base) with 5 μg · ml‐1 epinephrine freshly added (Group CO2 = 13 patients) or 20 ml of 2% lidocaine hydrochloride (17.3 mg · ml‐1 lidocaine base) also with 5 μg · ml‐1 epinephrine freshly added. Following clampage of the umbilical cord (at 40.1 ± 4.9 min after the injection of lidocaine for the CO2 group and at 41.0 ± 5.4 min for the HCl group), serum concentrations of lidocaine were measured both in the mother and in the umbilical vein. All newborns were examined by the same blinded pediatrician with Apgar scores at 1, 5 and 10 min and with Neurobehavioral Adaptive Capacity Scores (NACS) at 15 min, 2 h and 24 h. The concentrations of lidocaine in the serum were comparable in both groups: in the mothers 8.61 ± 1.48 μmol · l‐1 for the CO2 group vs 8.04 ± 2.36 μmol · l‐1 for the HCl group and in the newborns 3.86 ± 0.84 μmol · l‐1 for the CO2 group vs 3.92 ± 0.95 μmol · l‐1 for the HCl group. The ratio of umbilical vein to maternal vein concentrations of lidocaine was also similar in both groups: 0.45 ± 0.07 for the CO2 group vs 0.54 ± 0.24 for the HCl group. The percentage of newborns with a normal NACS (score ± 35/40) was equal in both groups, i.e. 91% at 15 min and 2 h of life and 100% at 24 h of life. We conclude that both lidocaine solutions are similar with respect to their transplacental passage and their effects on the neonatal neurobehavioral performance, and that both are safe when used for cesarean section in normal term pregnancy since the majority of newborns (91%) had a normal NACS (score ± 35/40), even at the first evaluation at 15 min of life.