Randomized clinical trial of preoperative dexamethasone on postoperative nausea and vomiting after laparoscopy for suspected appendicitis.

BACKGROUND: Few studies have investigated the effects of preoperative dexamethasone in acute surgical patients. This study examined the effects of 8 mg dexamethasone administered intravenously 30 min before surgery for suspected acute appendicitis. METHODS: A multicentre, parallel-group, double-blind, placebo-controlled study was conducted at two university hospitals in Denmark. Adults undergoing laparoscopic surgery for suspected appendicitis were eligible for inclusion. Participants, healthcare staff and investigators were blinded until all data analysis had been done. The primary outcome was the incidence of postoperative nausea and vomiting (PONV) during the first postoperative day. Secondary outcomes were pain, fatigue, sleep, opioid consumption, use of antiemetics, quality of recovery and duration of convalescence. Analysis was done according to the intention-to-treat principle. RESULTS: A total of 120 patients were enrolled; 57 patients in the dexamethasone group and 59 in the placebo group were eligible for primary analysis. In the dexamethasone group, 47 (95 per cent c.i. 35 to 60) per cent of patients experienced PONV compared with 63 (50 to 74) per cent) in the placebo group. The absolute risk reduction in PONV was 15 (-3 to 33) per cent in favour of the dexamethasone group (P = 0·098). Patients in the dexamethasone group had less pain at rest (difference in score on visual analogue scale (VAS) 9 (95 per cent c.i. 1 to 17) mm; P = 0·024), were less fatigued (difference in VAS score 7 (0 to 14) mm; P = 0·038), used fewer opioids (absolute risk reduction 17 (2 to 33) per cent; P = 0·033) and had better quality of recovery (difference in QoR-15 score 13 (4 to 22); P = 0·006) during the first postoperative day. There was no difference in postoperative complications (P = 0·595). CONCLUSION: Preoperative dexamethasone did not reduce PONV by the target level of 50 per cent. Registration number: NCT02415335 ( http://www.clinicaltrials.gov).

Effect of ketoprofen and its enantiomers on the renal disposition of methotrexate in the isolated perfused rat kidney.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit the renal tubular secretion of methotrexate. However, the relative contribution of the active S- and inactive R-enantiomers is unknown. This study examined the effect of racemic ketoprofen and its enantiomers on the renal disposition of methotrexate in the isolated perfused rat kidney (IPK). Nineteen kidneys were divided between a control and three treatment groups. Controls were perfused with methotrexate alone (25 micrograms mL-1, n = 5) over three 30-min periods. Treatment groups were perfused with methotrexate (25 micrograms m-1) for the first period, followed by a second period of methotrexate (25 micrograms mL-1) plus R- (n = 5), S- (n = 5) or RS-ketoprofen (n = 4) at 25 micrograms mL-1, and a third period of methotrexate (25 micrograms mL-1) plus R-, S- or RS-ketoprofen (50 micrograms mL-1). Perfusate and urine were collected over 10-min intervals. Methotrexate was measured by HPLC and its binding in perfusate by ultrafiltration. The clearance ratio (CR) for methotrexate was obtained by dividing the renal clearance by the product of its fraction unbound and the glomerular filtration rate. During control experiments, there was no significant change in the CR over 90 min. R-, S- and RS-ketoprofen at 50 micrograms mL-1 reduced the CR of methotrexate significantly, but there was no difference between the three groups. While the enantiomers of ketoprofen reduced the renal excretion of methotrexate, the interaction was not enantioselective.

Evaluation of side effects due to clozapine in long-term treatment of psychosis.

17 patients (13 males and 4 females) were examined for side effects due to long-term treatment with 8-chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo(b,e)(1,4)diazepine (clozapine) with emphasis on alterations in bone marrow, liver, and kidney function. 16 patients were schizophrenic, one patient was diagnosed psychosis e causa dubia. The age range was 25-68 years, with an average of 38.2 years. The daily clozapine dose varied from 225 to 800 mg with a total intake during the trial period of 149.1-891.6 g yielding an average of 479.8 g. The treatment period varied from 20 to 51 months, with an average of 35.9 months. None of the patients had to discontinue the treatment because of side effects. The laboratory data including hematological, and nephrological parameters revealed no significant changes related to clozapine treatment within the treatment period. No changes were observed in ECG. 12 patients experienced side effects, 8 of them receiving concomitant psycholeptic medication. 9 patients complained of temporary fatigue and 5 of these experienced continuous drowsiness. There were 8 cases of nocturnal hypersalivation and two cases of increased appetite. One patient developed light tachycardia and one patient orthostatic hypotension. Clozapine is known to be an effective anti-psychotic drug, but due to reports of agranulocytosis in 16 Finnish patients the drug was withdrawn from the Danish market in 1975 although later its use was merely restricted to special cases. This study does not indicate that clozapine contains greater risk of clinical side effects than commonly used psycholeptic drugs.

Additional studies on side effects of melperone in long-term therapy for 1 to 15 years in psychiatric patients.

The present study which reports on the hitherto longest continuous melperone treatment recorded in the literature, was conducted in order to reveal side effects of long-term melperone therapy. 17 female and 20 male patients, aged 33-97 years, most of them with the diagnoses: schizophrenia (11 patients), dementia organica (11 patients) and dementia senilis (11 patients) were treated with melperone (Buronil) in doses of 15--800 mg/day for 1 to 15 years. The patients were examined for clinical side effects, abnormal electrocardiograms and ophthalmological diseases as well as abnormal values in sedimentation rate, hemoglobin, leucocytes, creatinine, alanine-aminotransferase, gamma-glutamyl-transferase and bilirubin. Also the thymol reaction was done. The electrocardiograms and laboratory investigations were controlled by specialists in internal medicine and the eye diseases by an ophthalmologist. We did not find any severe side effects which could be related with any certainty to melperone therapy.

Additional studies on side effects of melperone in long-term therapy for 1-20 years in psychiatric patients.

The present study reporting on continuous melperone treatment of hitherto longest duration recorded in literature was conducted in order to reveal side effects of long-term melperone therapy. 50 patients, 24 females and 26 males, aged 37-102 (average: 81 years of age) were treated with melperone (Buronil, Bunil, Eunerpan) for 1 to 20 years. In most patients, daily dosage varied from 10 to 300 mg, total dosage ranging from 6510 mg to 1 662 225 mg, avr. 203 923 mg. Diagnoses were as follows: senile dementia (14), organic dementia (9), arterio-sclerotic dementia (8), schizophrenia (17) and nonspecific psychosis (2). The patients were examined for clinical side effects including abnormal ECGs and ophthalmological diseases. Biochemical laboratory tests comprised sedimentation rate, haemoglobin, leucocytes, creatinine, alanine-aminotransferase, gamma-glutamyl-transferase and bilirubin. The results were evaluated by a specialist in internal medicine and an ophthalmologist performed the examinations on the 20 patients who were able to cooperate. The conclusion was that no serious side effects were observed which could with any certainty be related to melperone therapy.