Use of tricyclic antidepressants as analgesic adjuvants results in nonhazardous prolongation of the QTc interval.

BACKGROUND: Tricyclic antidepressants (TCAs) are known to prolong QTc interval. However, little is known about the QTc lengthening effect of TCAs at analgesic dosages and the predictive factors for abnormal QTc prolongation. METHODS: We conducted a single-center, retrospective observational study, and evaluated 87 patients (65 amitriptyline, 22 nortriptyline) who underwent 12-lead electrocardiogram (ECG) examinations both before and after receiving TCAs for herpes zoster pain or postherpetic neuralgia from May 2007 to January 2012. Data on QTc interval, age, gender, the type and daily dosage of TCAs, the medication period until the second ECG examination, and ECG findings were obtained from electronic medical charts. RESULTS: The median daily dosages were 25 mg/day for amitriptyline and 10 mg/day for nortriptyline. The median medication period for all participants was 62 days. TCAs significantly prolonged the QTc interval (before, 413.2 +/-17.0 ms; after, 419.9 +/- 18.9 ms, p < 0.01). Three patients showed marked QTc prolongation, but it did not exceed 500 ms, or deltaQTc of 60 ms, and none had an episode of fatal arrhythmia. Univariate logistic regression analysis revealed left ventricular hypertrophy (LVH) to be the sole risk factor for abnormal QTc prolongation. The adjusted odds ratio was 4.09 (95% CI, 1.01-16.55, p < 0.05) by multivariate logistic regression analysis. CONCLUSIONS: TCAs as analgesic adjuvant significantly prolonged the QTc interval, but within an acceptable range. LVH was a significant predictor of abnormal QTc prolongation.

A delayed case of tension pneumopericardium after total gastrectomy.

A case of tension pneumopericardium that occurred after total gastrectomy in an 80 year old woman is presented. There have been some prior case reports of pneumopericardium that occurred during positive pressure ventilation; in this patient hypotension due to tension pneumopericardium occurred after extubation. Return of spontaneous ventilation with negative-pressure breathing may have induced air aspiration into the pericardial sac from the abdominal cavity.

Pharmacokinetics of lidocaine, bupivacaine, and levobupivacaine in plasma and brain in awake rats.

BACKGROUND: We have compared the pharmacokinetics and brain distribution of lidocaine, racemic bupivacaine (bupivacaine), and levobupivacaine in awake, spontaneously breathing rats. METHODS: Lidocaine (0.5 mg x kg x min), bupivacaine (0.1 mg x kg x min), or levobupivacaine (0.1 mg x kg x min) was continuously administered to rats for 2 h (n = 12, each anesthetic). Blood samples and cerebral dialysate were collected during infusion and for 2 h after termination of infusion. Concentrations of anesthetics in the cerebral extracellular fluid were measured by microdialysis using the retrodialysis calibration method. Tissue-to-plasma partition coefficients calculated from the total (protein-bound and unbound) and unbound concentrations in plasma and brain as well as pharmacokinetic parameters in plasma and cerebral extracellular fluid were compared among the three anesthetics. RESULTS: There were no differences in plasma total or unbound concentrations between bupivacaine and levobupivacaine. Concentrations of bupivacaine in the cerebral extracellular fluid were significantly higher than levobupivacaine (P < 0.001). Despite no differences in the ratio of total brain concentration to total plasma concentration among the three anesthetics, the ratio of cerebral extracellular fluid concentration to plasma unbound fraction of bupivacaine was significantly higher than lidocaine and levobupivacaine (0.58 +/- 0.09, 0.47 +/- 0.18, and 0.40 +/- 0.09, respectively; P = 0.03 and 0.003, respectively). CONCLUSIONS: Although the ratio of total brain concentration to total plasma concentrations of lidocaine, bupivacaine, and levobupivacaine was similar, concentration ratio of bupivacaine in the cerebral extracellular fluid to plasma unbound fraction was significantly higher than lidocaine and levobupivacaine.

[Prolonged pain after left hepatectomy].

We have experienced a patient complaining of the prolonged pain after left hepatectomy. The patient was a 53-year-old man. He underwent left hepatectomy for cholangiocellular carcinoma, and complained of prolonged abdominal pain for more than 10 days after the operation. After detailed examinations, we noticed duodenal perforation. After the conservative treatment, his pain was improved. In this case, the causes of the prolonged pain might be peritoneal irritation caused by gastric contents and duodenal perforation. The peritoneal irritation was caused by bile leakage and the deformity of the stomach that might be due to the enlarged dead space after left hepatectomy. We should be cautious of possible pyloric obstruction as the cause of prolonged pain after left hepatectomy.

Propranolol increases the threshold for lidocaine-induced convulsions in awake rats: a direct effect on the brain.

BACKGROUND: Propranolol is a beta-adrenoceptor antagonist used clinically. Local anesthetics are used for controlling pain, whereas propranolol is concomitantly given to treat hypertension and tachycardia. However, there are few studies examining the effects of propranolol on the toxicity of local anesthetics. We investigated the effect of propranolol on lidocaine-induced convulsions in awake, spontaneously breathing rats. METHODS: Male Sprague-Dawley rats were randomly divided into six groups (n = 8, each group). Rats were pretreated with intracerebroventricular saline (cerebroventricle-control: CV-C group), 10 or 30 microg/kg of (S)-(-)-propranolol (propranolol) (cerebroventricle-small dose: CV-S and cerebroventricle-large dose: CV-L groups, respectively) or i.v. saline (IV-control: IV-C group), 1 or 3 mg/kg of propranolol (IV-small dose: IV-S and IV-large dose: IV-L groups, respectively). Three minutes later, lidocaine was administered i.v. at 4 mg x kg(-1) x min(-1) until tonic-clonic convulsions occurred. RESULTS: The convulsive dose of lidocaine in the CV-L group was significantly larger than that in the CV-C group (30.6 +/- 5.1 vs 23.5 +/- 2.2 mg/kg, respectively, P = 0.008). Plasma concentrations of total and protein-unbound lidocaine, concentrations of lidocaine in the brain at the onset of convulsions were also significantly higher in the CV-L group than those in the CV-C group (36.1 +/- 4.8 vs 26.0 +/- 3.8 microg/mL, 22.5 +/- 3.5 vs 13.7 +/- 2.6 microg/mL, 82.7 +/- 7.1 vs 57.3 +/- 5.7 microg/g, P < 0.001 for all). The convulsive dose, plasma concentrations of total and protein-unbound lidocaine, and brain lidocaine in the IV-L group were also significantly larger than those in IV-C group and comparable with those in the CV-L group. The plasma concentration of propranolol before starting an infusion of lidocaine in the IV-L group was approximately 60-fold higher than that in the CV-L group (554.7 +/- 104.6 and 9.3 +/- 6.7 ng/mL, respectively). CONCLUSIONS: Propranolol increased the threshold for lidocaine-induced convulsions by directly acting on the brain.

[The use of questionnaires for rotating residents in evaluating training in anesthesiology].

BACKGROUND: We prepared questionnaires for the rotating residents during their assignment for anesthesiology in the novel Japanese residency programs for the year 2004. METHODS: Questionnaires consisting of 39 items with 235 model answers for these items were prepared. The residents underwent three interviews by these questionnaires over the three-month training period. The number of correct answers for these questionnaires was recorded and evaluated using a computer database software. RESULTS: There was no significant correlation between the results of these questionnaires and the subjective evaluation by supervisors conducted during clinical training. On stepwise regression analysis, the results of the questionnaires for "American Society of Anesthesiologists Physical Status", "contraindications for epidural anesthesia", "complications of general anesthesia" and "initial procedures for patients in the operating room" correlated with the subjective evaluation by supervisors. CONCLUSIONS: Stepwise regression analysis was shown to be helpful in improving the questionnaires regarding the training in anesthesiology.

Nitrous oxide induces paradoxical electroencephalographic changes after tracheal intubation during isoflurane and sevoflurane anesthesia.

In this randomized, double-blind, controlled study, we tested the hypothesis that nitrous oxide (N2O) affects bispectral index (BIS) and 95% spectral edge frequency (SEF95) in response to tracheal intubation during anesthesia with isoflurane and sevoflurane. In protocol 1, we randomly allocated 90 ASA physical status I patients to 6 groups (n = 15 each). Anesthesia was induced with isoflurane or sevoflurane with 0%, 33%, or 66% N2O. The concentration of isoflurane and sevoflurane was gradually increased and end-tidal concentrations were maintained at 1.1% and 1.7%, respectively. Tracheal intubation was performed 12 min after induction of anesthesia. BIS was significantly increased 1 min after tracheal intubation compared before laryngoscopy in patients receiving only isoflurane or sevoflurane (P = 0.001 and 0.007, respectively). In patients receiving 66% N2O-isoflurane or 66% N2O-sevoflurane, both BIS and SEF95 were significantly decreased after tracheal intubation and significantly lower than in those patients receiving only isoflurane or sevoflurane, respectively (P < 0.01 for both). In protocol 2, 3 microg/kg of IV fentanyl completely abolished the decrease of BIS and SEF95 after tracheal intubation during anesthesia with 66% N2O-isoflurane and 66% N2O-sevoflurane (n = 10). We conclude that 66% N2O induced a paradoxical decrease of BIS in response to tracheal intubation during anesthesia with isoflurane and sevoflurane.

The short-acting beta1-adrenoceptor antagonists esmolol and landiolol suppress the bispectral index response to tracheal intubation during sevoflurane anesthesia.

In this randomized, double-blind, controlled study, we tested the hypothesis that the short-acting beta(1)-adrenoceptor antagonists esmolol and landiolol suppress hemodynamic changes and bispectral index (BIS) increases, both of which are induced by tracheal intubation under general anesthesia with sevoflurane alone. Forty-five patients were randomly assigned to the control, esmolol, and landiolol groups (n = 15 each). Anesthesia was induced with sevoflurane in oxygen, with an end-tidal concentration maintained at 1 minimum alveolar anesthetic concentration (MAC). Infusion of saline (control group), esmolol (bolus of 1 mg/kg and then 0.25 mg x kg(-1) x min(-1); esmolol group), or landiolol (bolus of 0.125 mg/kg and then 0.04 mg x kg(-1) x min(-1); landiolol group) was started 5 min after the induction of anesthesia and was continued throughout the study. Tracheal intubation was performed 12 min after anesthesia induction. There were no differences in overall changes of mean arterial blood pressure among the three groups, whereas, at 1-5 min after tracheal intubation, heart rate increased in all groups but was significantly slower in the esmolol and landiolol groups than in the control group (P < 0.05). BIS was between 96 and 98 for all patients at baseline and decreased during the induction of anesthesia. There were no differences in BIS among the three groups before laryngoscopy (39 +/- 5, 39 +/- 5, and 38 +/- 4 in the control, esmolol, and landiolol groups, respectively). BIS increased significantly in the control group (54 +/- 10; P < 0.05) 1 min after intubation, whereas it remained unchanged in the esmolol and landiolol groups (45 +/- 10 and 41 +/- 6, respectively). In conclusion, the increase in both heart rate and BIS after tracheal intubation under 1 MAC sevoflurane anesthesia was suppressed by the concomitant administration of either esmolol or landiolol.