Contemporary strategies to preserve renal function during cardiac and vascular surgery.

Mortality rates associated with perioperative acute renal failure (ARF) range from 60% to 90%. The major causes of ARF are prerenal factors that decrease renal blood flow; intrarenal factors that have a direct effect on tubules, interstitium, or glomeruli; and postrenal factors that obstruct urine outflow. Current strategies to provide perioperative renal protection include maintaining adequate renal O2 delivery, suppressing renovascular vasoconstriction, renovascular vasodilatation, maintaining tubular flow, decreasing renal cellular O2 consumption, and attenuating reperfusion injury. A study of patients undergoing elective repair of a thoracoabdominal aortic aneurysm (TAAA) found that the use of the selective dopamine-1 receptor agonist fenoldopam was associated with reductions in mortality, dialysis requirements, and lengths of stay in the hospital and intensive care unit. The study authors suggest that the improved patient outcomes and hospital-utilization data resulting from the use of fenoldopam were directly related to the protection of renal function during surgery and a reduction of postoperative renal complications.

Glycosylated and non-glycosylated prolactin forms are increased after opioid administration as part of surgical anaesthesia.

OBJECTIVE: Previous studies have shown that non-glycosylated prolactin (NG-PRL) increased more markedly than glycosylated hormone (G-PRL) after TRH or metoclopramide stimulation. The aim of the present study was to determine whether such results could be extended to opioid-induced PRL stimulation. DESIGN: Open and prospective study. Using a newly developed IRMA specific for NG-PRL, we determined G-PRL and NG-PRL immunoreactivities after administration of 0.8-1.2 mg of the opioid drug phenoperidine as part of an anaesthesia. PATIENTS: Ten male patients anaesthetized for surgical treatment of a prolapsed lumbar intervertebral disc. MEASUREMENTS: Samples were obtained hourly pre and post-operatively, and every 15 minutes during operation for determination of plasma PRL, NG-PRL and G-PRL. Plasma cortisol, ACTH and GH levels were measured in an attempt to differentiate the respective roles of stress and opiate agonists in the variations of PRL levels during surgery. RESULTS: A dramatic increase in PRL levels was observed in all patients from an average of 300 +/- 90 to 1200 +/- 330 mU/l (mean + SEM) 30 minutes after drug administration. The proportion of G-PRL immunoreactivity was not significantly different when basal (25.2%) and stimulated (27%) values were compared (P > 0.05), and when mean increments of NG-PRL and G-PRL were compared (345 and 348%, respectively). The opioid drug induced a significant decrease in cortisol levels after injection and during operation (from 585 +/- 63 to 99 +/- 51 nmol/l) with a concomitant decrease in ACTH levels. GH levels were not significantly altered during anaesthesia but were significantly greater (P < 0.05) after than before surgery (5.0 +/- 1.3 vs 0.98 +/- 0.54 mU/l, respectively). CONCLUSIONS: We conclude from the present and from previous data that opioid induced anaesthesia is accompanied by an increase in both glycosylated and non-glycosylated PRL and that different PRL secretagogues may induce distinct responses in terms of PRL molecular forms.

The absence of teratogenic effects of some analgesics used in anaesthesia. Additional evidence from a mouse model.

The possibility exists that agents used in anaesthesia may have adverse teratogenic effects on staff, patients, and developing fetuses. It has been shown that a range of neurotropic drugs, when injected into pregnant mice on the 9th day of gestation, produce a characteristic group of central nervous system malformations in their fetuses. We have studied the possible teratogenicity of pethidine, fentanyl, phenoperidine and lignocaine when tested in this way and conclude that they appear to have less effect than other neurotropic drugs previously tested.

[Pediatric anesthesia and pharmacokinetics of propofol administered at a constant rate]. / Anesthésie pédiatrique et pharmacocinétique du propofol administré a débit constant.

The pharmacokinetic properties of propofol given at a constant rate, were studied in 10 children. Propofol was administered at a dose according to I.C.I. Pharma advices. For minor surgery, a low quality of general anesthesia was observed in correlation with low plasma levels of propofol. An increase in dosage would be necessary in children above 8 years old.

Simultaneous determination of pethidine (meperidine), phenoperidine, and norpethidine (normeperidine), their common metabolite, by gas chromatography with selective nitrogen detection.

This article describes a selective gas chromatographic method for the resolution and quantification of phenoperidine and its two metabolites, pethidine (meperidine) and norpethidine (normeperidine). Drugs and SKF 525 A, the internal standard, are separated from plasma by solvent extraction under alkaline conditions. They are chromatographed on a 3% OV-17 Chromosorb Q glass column and detected with a nitrogen-phosphorous detector. Linearity is observed in the study range (5-200 ng/ml). No interference by endogenous substances is noted.

Early extubation after coronary artery surgery in efficiently rewarmed patients: a postoperative comparison of opioid anesthesia versus inhalational anesthesia and thoracic epidural analgesia.

Twenty-eight patients were studied after uncomplicated aortocoronary bypass surgery with hypothermic cardiopulmonary bypass (CPB). In all patients residual hypothermia was effectively treated by the use of extended rewarming during CPB and postoperatively by an external heat source. This treatment almost eliminated postoperative shivering, and it resulted in the lowering of oxygen uptake, carbon dioxide production, and required ventilatory volumes to stable levels where spontaneous breathing could be used safely. The patients were divided into two groups. In group I (n = 12), intraoperative anesthesia was based on an intravenous (IV) opioid (phenoperidine), which caused persistent respiratory depression and made mechanical ventilation necessary for a mean postoperative time period of 10.7 +/- 3.8 hours even with the rewarming. In group II (n = 16), thoracic epidural analgesia and intraoperative general anesthesia with enflurane were used. In this group, postoperative metabolic and ventilatory requirements were stable and low, finger skin temperature was normalized earlier, systemic vascular resistance was lower, and stroke index was higher. Emergence from anesthesia was uneventful and was achieved early postoperatively in Group II. The patients had good pain relief and were mentally alert. Adequate spontaneous breathing was resumed quickly and endotracheal extubation was performed within the first two postoperative hours (1.6 +/- 0.5 hours). No complications or increased morbidity occurred, and no patient needed to be reintubated in Group II.

[Phenoperidine: pharmacology and use in pediatric resuscitation]. / La phénopéridine: pharmacologie et utilisation en réanimation pédiatrique.

Phenoperidine is mainly metabolised in the liver, and has a biliary and urinary elimination. Because its analgesic effects are fast and prolonged, this drug is often used in pediatric intensive care units, due to its interesting pharmacologic properties (mild cardiac and respiratory depression).

Influence of bolus doses of phenoperidine on intracranial pressure and systemic arterial pressure in traumatic coma.

The effects of bolus doses of phenoperidine 1-2 mg i.v. either alone, or combined with pancuronium 2-4 mg, were investigated in seven patients in traumatic coma. Phenoperidine alone significantly reduced mean arterial pressure (MAP) by a mean (+/- SEM) of 13.2 (+/- 2.8) mm Hg. Overall there was no significant change in intracranial pressure (ICP) despite the decreases in MAP and, consequently, cerebral perfusion pressure (CPP) decreased (14.0 +/- 2.4 mm Hg) on all but one occasion. In some instances these decreases were considerable (maximum 38 mm Hg). Similar results were obtained when phenoperidine was combined with pancuronium. These findings suggest that the bolus administration of phenoperidine and probably other opiates should be avoided in traumatic coma.

Double-blind comparison of the efficacy of extradural diamorphine, extradural phenoperidine and i.m. diamorphine following caesarean section.

A randomized, double-blind study of the efficacy, duration of action and side effects of three analgesic regimens following Caesarean section is described. Patients received i.m. diamorphine 5 mg, extradural phenoperidine 2 mg or extradural diamorphine 5 mg. Analgesia was of rapid onset in all groups, as judged by reductions in linear analogue pain scores and rank pain scores. Time to next analgesia was significantly greater after extradural phenoperidine (5.96 h) and extradural diamorphine (8.39 h) than after i.m. diamorphine (3.40 h) (P less than 0.001). Itching was reported on direct questioning by 50% of patients in the extradural groups. No serious side effects were reported. Factors affecting the disposition of extradurally administered diamorphine are discussed.

[Hemodynamic parameters and blood-free surgical field with nitroglycerin in maxillofacial surgery]. / Paramètres hémodynamiques et exsanguinité du champ opératoire sous nitroglycérine en chirurgie maxillo-faciale.

73 oral facial surgery have been performed using controlled-hypotension induced with nitroglycerin (NTG) to reduce surgical bleeding. Surgical bleeding has been reduced in more than 45% of cases. But frequent lack of correlation between blood pressure, heart beat and bleeding might imply vascular reflex mechanisms induced by controlled-hypotension using NTG. Hemodynamic parameters such as blood pressure and heart rate seem to be insufficient to monitor controlled hypotension efficiency on surgical bleeding. The use of peroperative tissues blood flow monitoring may help for the better understanding of surgical bleeding during controlled-hypotension using NTG.

Pharmacokinetics of phenoperidine in anaesthetized patients undergoing general surgery.

The pharmacokinetics of phenoperidine have been studied in five anaesthetized patients receiving a 2-mg bolus dose i.v. Plasma concentrations were measured using a sensitive radioimmunoassay method. The distribution of phenoperidine was described according to a two-compartment open model. The mean distribution half-life (T1/2 alpha) for the five patients was short (2.2 min); the mean elimination half-life (T1/2 beta) was 193 min. The mean whole body clearance was 22 ml min-1 kg-1 and the apparent steady state distribution volume (VSS) was 5.7 litre kg-1. Secondary concentration peaks occurred in all patients; in two patients these were substantial and occurred 80 min after injection.

Pharmacokinetics of phenoperidine in patients undergoing cardiopulmonary bypass.

Phenoperidine concentrations were studied, using radioimmunoassay, in five patients submitted to coronary artery bypass graft surgery. Administration of phenoperidine consisted of a 5-mg bolus dose followed by constant infusion of 5 mg h-1. Before cardiopulmonary bypass, phenoperidine concentrations were stable in an individual patient, but there was a large scatter between patients. The concentrations decreased immediately following the start of the bypass, but this decrease was short. During cardiopulmonary bypass, the phenoperidine concentrations increased progressively and were greater at the end of the bypass than before it. The increase in concentration continued following the discontinuation of bypass. The ratios of change of the observed results were in accord with a theoretical evaluation, although the observed concentrations were all greater than those calculated, except at one point. This difference in phenoperidine concentration is probably related to an alteration of liver plasma flow. Haemodilution as a result of the priming of the cardiopulmonary bypass circuit played only a transient role.