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We have investigated the use of alfentanil by infusion to sedate 14 patients during controlled ventilation on the intensive therapy unit (ITU). An initial rate of 24 micrograms.kg-1.h-1 was chosen and altered thereafter according to patient response. Incremental doses of midazolam (2.5-5.0 mg) were given intravenously (i.v.) if indicated. In 4 patients, the use of a muscle relaxant was necessary to allow adequate controlled ventilation of the patient. The mean duration of infusion was 27.9 h (range 10-141 h), and the mean total dose of alfentanil was 69.3 mg (12.5-240 mg). Spontaneous ventilation was rapidly achieved in 11 patients after stopping the infusion. The mean arterial carbon dioxide tension (PaCO2) was 5.38 kPa, 15-30 min after stopping the infusion. The clinical condition of 2 patients necessitated a change in sedation technique and one patient died during the alfentanil infusion. Alfentanil by infusion caused no major cardiovascular effects and did not influence the plasma cortisol response to trauma. There was no major alteration in blood biochemistry or haematology during the infusions of alfentanil. The plasma concentrations of alfentanil during infusion showed a wide variability. These probably relate to both changes in the volume of distribution of the drug and in hepatic clearance.

The hemodynamic effects of methohexital, at infusion rates of 60-65 and 120 micrograms/kg/min with concomitant inhalation of 67% nitrous oxide in oxygen, have been studied during spontaneous and controlled ventilation in 8 patients. Under most of the conditions studied methohexital infusion anesthesia was associated with lower arterial pressure (-13% to -33%) than in the awake state, decreased cardiac output (-26% to -38%), and increased systemic vascular resistance (+5% to +37%) during surgery, but also with decreased cardiac output (-25%) and decreased systemic vascular resistance (-13%) during anesthesia without surgery. The higher infusion rate was not associated with decreases in arterial pressure or cardiac output during either spontaneous or controlled ventilation. The hemodynamic response to laryngoscopy and intubation was poorly suppressed by methohexital in that peak arterial pressures exceeded the preanesthetic values by 33%. No evidence of impaired hepatocellular function was found after infusions of methohexital lasting up to 4 h.

Summary This study investigated the effects of etomidate on endocrine responses to anaesthesia and surgery. Patients undergoing abdominal hysterectomy received standard anaesthetics of either etomidate for induction with etomidate infusion, or thiopentone and halo thane. Etomidate suppressed the secretion of cortisol and aldosterone for between 8 and 22 hours after the end of the etomidate infusion; 11-deoxycortisol secretion was not suppressed during the etomidate infusion, but rose postoperatively; 17α-hydroxyprogesterone suppression also lasted only as long as the etomidate infiion. There were no effects on plasma oestradiol, A CTH, or prolactin, but growth hormone concentrations were elevated in the etomidate group. Etomidate was concluded to have influenced adrenocortical function only, where it probably inhibits 11 β-hydroxylation, 17 α-hydroxylation and other intramitochondrial hydroxylation reactions. There were no clinical sequelae attributable to adrenocortical suppression. The relationship of chemical structure of etomidate and other phenylated imidazoles to inhibition of steroidogenesis is discussed.

Summary The use of intravenous anaesthetic agents by continuous infusion requires knowledge of their pharmacokinetic properties. In this article, the general pharmacokinetic principles behind the use of infusions of intravenous agents are presented and the literature with regard to the individual drugs used in this way is reviewed.

Minaxolone has been used for the induction and maintenance of anaesthesia in 60 patients undergoing minor surgical procedures. With nitrous oxide as the only supplement, satisfactory conditions were obtained in 56 patients. Patient acceptance was high.

Buprenorphine 0.3 mg and papaveretum 20 mg, both combined with hyoscine 0.4 mg, were used is premedicants in female patients undergoing laparoscopy or abdominal hysterectomy. The effects were compared. It was found that the increase in drowsiness and tranquillity was greater following buprenorphine than that following papaveretum. A low frequency of nausea was reported in the buprenorphine-hyoscine group of patients who had undergone hysterectomy. The analgesic effects of the drugs, in these doses, appeared to be similar in degree and duration.

Thirty paired samples of plasma and whole hemolyzed blood were obtained from patients undergoing surgery. Morphine concentrations were measured with the DPC serum morphine kit without prior treatment. In a regression analysis, the equation to the regression line was blood = 1.02 plasma + 1.0 ng/mL, and the correlation coefficient was 0.994. Radioimmunoassay screening of postmortem blood samples can be performed without prior sample treatment.

Plasma concentrations after intravenous morphine were measured by a specific radioimmunoassay method in patients undergoing renal transplantation and in control subjects. In both transplant patients and controls, plasma morphine fell in the first 10 min, but there was no significant further fall in the transplant patients until between 3 and 5 hr, when there was an abrupt reversion to the same elimination t½ as the controls. This coincided with recovery of renal function after the period of cold ischemia. In the transplant patients the AUC over 24 hr was higher and the plasma clearance was lower than in controls. The role of the kidney in morphine elimination is discussed. Clinical Pharmacology and Therapeutics (1984) 35, 641–645; doi:10.1038/clpt.1984.88

Morphine plasma concentrations were determined in six patients receiving kidney transplants from living-related donors, and nine patients receiving kidney transplants from cadavers. The total cold ischemic time was about 2 hr for kidneys from living-related donors and 14 hr for those from cadavers.

Intravenous morphine infusions were given to 20 patients in the intensive-care unit to provide sedation and analgesia. In 10 of the patients renal impairment was already present or developed during intensive care. Plasma morphine concentrations for a given dose of morphine and morphine clearance depended on renal function; dose-related plasma morphine concentrations rose as renal function deteriorated. Reduced morphine clearance leads to increased elimination half-life of the drug, and neurological impairment caused by unrecognised high concentrations of morphine could result in an incorrect diagnosis of cerebral damage in patients in intensive care.