C. Prys-Roberts

Induction and maintenance of propofol anaesthesia.: A manual infusion scheme

A simple, manually controlled infusion scheme for continuous administration of propofol was derived by simulation of a computer algorithm designed to achieve a predetermined blood concentration of propofol within 2 minutes and to maintain a constant blood level for the duration of surgery. The manual infusion scheme for a target blood propofol concentration of 3 μg/ml, consisted of a loading dose of 1 mg/kg followed immediately by an infusion of 10 mg/kg/hour for 10 minutes, 8 mg/kg/hour for the next 10 minutes and 6 mg/kg/hour thereafter. An overall mean blood propofol concentration of 3.67 μg/ml was achieved within 2 minutes and maintained stable for the subsequent 80–90 minutes of surgery. The decrease of systolic and diastolic arterial pressures at induction was much less than that previously described after larger induction doses of propofol and there was a negligible haemodynamic response to largyngoscopy and intubation or to the subsequent surgery. The quality of induction and maintenance of anaesthesia was satisfactory in every patient.

INVOLVEMENT OF THE SYMPATHETIC NERVOUS SYSTEM IN TETANUS: Studies on 82 Cases

Abstract Retrospective studies are described on a series of 82 patients with tetanus, 44 of whom were treated by tracheostomy, curarisation, and intermittent positive-pressure ventilation. Patients with severe tetanus may develop a characteristic syndrome whose features include sustained but labile hypertension and tachycardia, irregularities of cardiac rhythm, peripheral vascular constriction, profuse sweating, pyrexia, increased carbon-dioxide output, increased urinary catecholamine excretion, and, in some cases, the late development of hypotension. It is argued that this syndrome may be due to continuous but fluctuating overactivity of the sympathetic nervous system.

A comparison of remifentanil and alfentanil in patients undergoing major abdominal surgery

The efficacy and safety of remifentanil and alfentanil for patients undergoing major abdominal surgery were compared. Premedicated patients received a loading dose of remifentanil (1.0 μg.kg−1; n =116) and a continuous infusion of 0.5 μg.kg−1.min−1, or a loading dose of alfentanil (25 μg.kg−1; n =118) and a continuous infusion of 1.0 μg.kg−1.min−1. Propofol was administered (10 mg every 10 s) until loss of consciousness. Patients’ lungs were ventilated with 66% nitrous oxide and 0.5% (end‐tidal) isoflurane in oxygen. The study drug infusion rate was reduced by 50% 5 min after intubation. Alfentanil was discontinued 15 min before the end of surgery, whereas remifentanil was continued in the immediate postoperative period at a reduced dose. Responses to intubation (28%) and skin incision (17%) occurred approximately twice as often in the alfentanil group (15% and 8%; p = 0.014 and p = 0.037, respectively). More patients receiving alfentanil had one or more responses to surgery (72% vs. 57%; p = 0.016). The time to spontaneous respiration, adequate respiration, response to verbal command and time to recovery room discharge were similar. However, owing to decreased variability, the time to extubation was shorter with remifentanil than with alfentanil (p =0.048). There was a similar overall incidence of adverse events in both groups, 82% and 75% of patients, respectively. Adverse events associated with remifentanil were rapidly controlled by dose reductions. The incidence of intra‐operative hypotension and bradycardia was higher in the remifentanil group (p ≤0.033). An initial remifentanil infusion rate of 0.1 μg.kg−1.min−1 titrated to individual need provided postoperative pain relief in the presence of adequate respiration in 71% of patients. When using remifentanil in the immediate postoperative setting, rapid administration of bolus doses and infusion rate increases resulted in a relatively high incidence of muscle rigidity, respiratory depression and apnoea. Changing the postoperative regimen to avoid rapid changes in remifentanil blood concentration resulted in more effective analgesia and dramatically reduced the incidence of adverse events during this period. In patients undergoing major abdominal surgery, remifentanil appears to offer superior intra‐operative haemodynamic stability during stressful surgical events compared with alfentanil without compromising recovery from anaesthesia. Remifentanil can be administered as a postoperative analgesic agent at a starting dose of 0.1 μg.kg−1.min−1; however, it should only be used in the presence of adequate supervision and monitoring of the patient. Administration of bolus doses is not recommended in this setting.

Hemodynamic effects of infusions of the emulsion formulation of propofol during nitrous oxide anesthesia in humans.

The hemodynamic response to anesthesia with the aqueous emulsion formulation of propofol was studied in healthy patients (ASA I or II), aged 39–57 yr, premedicated with morphine, 0.15 mg/kg. Anesthesia was induced in all patients with propofol, 2 mg/kg. Subsequently, patients were randomly assigned to two groups and maintained by a continuous intravenous infusion (group 1 received 54 μg·kg−1·min−1, group 2 received 108 μg·kg−1·min−1) to supplement 67% nitrous oxide. Three minutes after induction, systolic arterial pressure (SAP) decreased 28% (P < 0.01) and was associated with decreased (−12%) cardiac output (Q70) and decreased (−15%) systemic vascular resistance (SVR). The hemodynamic response to tracheal intubation was not obtunded, but peak values of arterial pressures and heart rate did not exceed those recorded awake. Thirty minutes elapsed before repeating measurements prior to the first surgical incision. In group 1, SAP and Q70 decreased to 65% and 68% of awake values and in group 2 to 55% and 74% (P < 0.05). Mild ventilatory depression persisted for the duration of spontaneous ventilation and was not reduced by the stimulus of surgery, which caused no significant hemodynamic responses in either group. Decreasing arterial Pco2 to the awake value by controlled ventilation increased SVR (P < 0.05), but the associated increased SAP and decreased Q70 did not reach statistical significance. No patient reported awareness. The infusion of the emulsion formulation of propofol was associated with satisfactory anesthesia and recovery and with hemodynamic effects similar to those recorded with other intravenous anesthetics.

Efficacy and safety of doxazosin for perioperative management of patients with pheochromocytoma.

Despite adverse side effects, phenoxybenzamine has been widely used for the preoperative management of patients with pheochromocytoma. Doxazosin, a specific a 1-adrenoceptor antagonist, has a pharmacologic profile more suited to controlling blood pressure in such patients. A sequential study of 35 patients with pheochromocytoma encompassed a definite and prescribed change in preoperative drug management from phenoxybenzamine to doxazosin. Hemodynamic, pharmacologic, and biochemical indicators of a- and b-adrenoceptor blockade were measured before, during, and after anesthesia and surgery in 8 patients pretreated with phenoxybenzamine and 27 patients pretreated with doxazosin. Doxazosin (2–16 mg/day) was as effective as phenoxybenzamine in controlling arterial pressure and heart rate before and during surgery, but doxazosin caused fewer undesirable side effects both before and after surgery. Following phenoxybenzamine therapy substantial a 1-adrenoceptor blockade, detected as a right shift of phenylephrine dose-response curves, persisted for more than 2 days postoperatively, whereas after doxazosin it was undetectable on the first postoperative day. Doxazosin provided safe, efficacious pre- and perioperative control of arterial pressure. In patients with predominantly norepinephrine-secreting tumors, pretreatment 24-hour urinary norepinephrine excretion gave an indication of the daily doxazosin requirement.

The effect of intravenous dexmedetomidine premedication on the dose requirement of propofol to induce loss of consciousness in patients receiving alfentanil

Dexmedetomidine reduces the dose requirements for opioids and anaesthetic agents. We conducted a single‐centre, open‐label, noncomparative phase II study of the effect of intravenous dexmedetomidine on the dose requirement of propofol to induce loss of consciousness in 49 ASA I and II patients. The initial dexmedetomidine infusion scheme was reduced twice because of adverse events. Forty patients who received the final infusion scheme were randomly allocated to receive one of five stepped propofol infusions; loss of consciousness was assessed after 21 min. The ED50 for the final infusion rate of propofol to suppress consciousness was 3.45 mg.kg−1.h−1 (95% CL 2.7–4.2): ED95 was 6.68 mg.kg−1.h−1 (95% CL 5.1–19.1), EC50 was 1.69 µg.ml−1 (95% CL 0.95–2.5) and EC95 was 5.7 µg.ml−1 (95% CL 3.2 to > 10). Our final dose of dexmedetomidine of 0.63 µg.kg−1 caused a reduction in the overall concentration and dose of propofol required to produce loss of consciousness, but no significant shift in the dose–response curve compared with other studies.

Effects of anesthesia on baroreflex control of heart rate in man.

The effects of anesthesia on the setting and sensitivity of baroreceptor reflex control of heart rate in man were studied. Modest increases in systemic arterial blood pressure were produced transiently by small amounts of phenylephrine intravenously. The quantitative relationship between individual systolic arterial pressure pulses and subsequent cardiac cycle lengths was evaluated as an index of reflex performance.Thiopental produced a decrease in baroreflex sensitivity, associated with tachycardia. Halo-thane and nitrous oxide resulted in marked reflex resetting, permitting the combination of bradycardia and reduced blood pressure. The mechanisms which may produce baroreflex resetting during anesthesia are discussed. We propose that barbiturate effects on heart rate control arc achieved primarily in the central nervous system, and perhaps at the heart itself. Halothane and nitrous oxide could operate at baroreceptor sites in addition.

Ventilatory depression related to plasma fentanyl concentrations during and after anesthesia in humans.

Twenty-four patients were allocated randomly into four groups for the study of the pharmacokinetics of, and effects on postoperative ventilation of, two doses of fentanyl (10 μg/kg or 25 μg/kg) administered at the start of general anesthesia in which ventilation was controlled at a fixed volume, but arterial PCO2 was adjusted to a range of either 38–42 torr, or 20–25 torr. During the first 2 hr after anesthesia, ventilatory depression (CO2 responsiveness decreased to <50% of awake values, PACO2 > 48 torr) occurred only in patients who had received 25 μg/kg fentanyl, and was more marked in patients who were hyperventilated to a low PACO2 during anesthesia. Plasma fentanyl concentrations associated with 50% depression of CO2 responsiveness were in the range 1.5–3.0 ng/ml, the lower values found in patients hyperventilated to a low PACO2. Whole-body clearance of fentanyl was significantly decreased by hypocapnic hyperventilation.

An assessment of the Dinamap 845.

The accuracy of the Dinamap 845 automatic blood pressure recorder was assessed by comparing its own indirect determinations of blood pressure with direct intra‐arterial recordings. It was found that in the majority of cases it was capable of producing reliable trend information during anaesthesia. The instrument may not be able to interpret pressure signals from a patient with a severe dysrhythmia. It is probably an unsuitable monitor for use with very rapidly acting drugs such as sodium nitroprusside.

Hemodynamic and Hepatic Effects of Methohexital Infusion during Nitrous Oxide Anesthesia in Humans

The hemodynamic effects of methohexital, at infusion rates of 60—65 and 120 μg/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.