M. Morgan

The haemodynamic effects of intravenous induction. Comparison of the effects of thiopentone and propofol.

The haemodynamic changes following induction of anaesthesia with equipotent doses of propofol and thiopentone have been compared. Propofol caused a significant fall in arterial blood pressure and total peripheral resistance, with a slight fall in cardiac output. There were no changes in heart rate. Apart from an initial, but statistically insignificant increase in heart rate, similar changes were produced by thiopentone, but to a lesser degree. It is concluded that induction of anaesthesia with propofol results in acceptable haemodynamic changes, but that the agent is more depressant to the cardiovascular system than thiopentone.

Propofol infusion for sedation in the intensive care unit: preliminary report.

Propofol (2,6,di-isopropylphenol) was given by continuous intravenous infusion to provide sedation after cardiac surgery in 30 patients and its effects compared with those of midazolam given to a further 30 patients. Propofol infusion allowed rapid and accurate control of the level of sedation, which was satisfactory for longer than with midazolam. Patients given propofol recovered significantly more rapidly from their sedation once they had fulfilled the criteria for weaning from artificial ventilation and as a result spent a significantly shorter time attached to a ventilator. There were no serious complications in either group. Both medical and nursing staff considered the propofol infusion to be superior to midazolam in these patients. These findings suggest that propofol is a suitable replacement for etomidate and alphaxalone-alphadolone for sedating patients receiving intensive care.

Effects of thiopentone, etomidate and propofol on the haemodynamic response to tracheal intubation

The haemodynamic response to tracheal intubation was compared in 303 patients in whom anaesthesia was induced with either thiopentone 4 mg/kg, etomidate 0.3 mg/kg or propofol 2.5 mg/kg, with and without fentanyl 2 μg/kg. There was after propofol alone a significant decrease in arterial blood pressure, which did not increase above control values after intubation. Significant increases in arterial pressure followed intubation in patients induced with thiopentone or etomidate alone. Increases in heart rate occurred with all agents after laryngoscopy. The use of fentanyl resulted in arterial pressures lower than those after the induction agent alone, and in an attentuation, but not abolition of the responses to largyngoscopy and intubation.

Ventilatory effects of propofol during induction of anaesthesia. Comparison with thiopentone.

The ventilatory effects of induction of anaesthesia with either propofol 2.5 mg/kg or thiopentone 4.0 mg/kg have been observed in patients premedicated with either atropine alone or papaveretum and hyoscine. Induction of anaesthesia with propofol was accompanied by a greater degree of ventilatory depression which was of longer duration than following thiopentone. The effect was accentuated by the opioid premedication.

Propofol for long-term sedation in the intensive care unit A comparison with papaveretum and midazolam*

Thirty‐seven patients with a wide range of illnesses were studied during mechanical ventilation of the lungs in an intensive care unit. Fifteen were sedated with a continuous propofol infusion, with analgesia provided by bolus doses of papaveretum. Twelve received a continuous infusion of papaveretum, supplemented by bolus doses of midazolam. The level of sedation was assessed every four hours and measurements were made of haemodynamic and respiratory variables. Levels of sedation were generally satisfactory in both groups. Six patients who received propofol required the use of muscle relaxants, because of their strong respiratory drives, to achieve synchronisation with the ventilator. There was no significant difference in respiratory or haemodynamic variables between the groups, but several patients required inotropic support because of their disease. There was no evidence of inhibition of adrenal steroidogenesis in the propofol group. Propofol can be a useful sedative agent in the intensive care unit, but sedative regimens should be tailored to individual patient requirements.

Cholinesterase Its significance in anaesthetic practice

Plasma cholinesterase is an enzyme which has importance to the anaesthetist primarily for its rôle in the metabolism of suxamethonium, although other anaesthetic related drugs that this enzyme metabolises are also increasingly important. In this article we review current thoughts on the function, profile and chemistry of plasma cholinesterase. Causes of variations in the activity of the enzyme are described and the basis of genetic variations is explained.

Nitrous oxide: time to stop laughing?

Dephlogisticated air (nitrous oxide) was discovered by Joseph Priestley in 1786 [1] when he noticed that ‘a candle burned in this air with a remarkably vigorous flame.’ He called it dephlogisticated air because of its ability to sustain combustion. Priestley assumed that the new gas had a propensity to absorb phlogiston that explained this observation (at the time phlogiston was thought to be the flammable part of any substance). The analgesic properties of this new gas were noted by Davy in his Researches, Chemical and Philosophical [2] in which he records how the inhalation of three or four breaths of the gas greatly relieved his toothache. He went on to conclude that ‘As nitrous oxide in its extensive operation appears capable of destroying physical pain, it may probably be used with advantage during surgical operations in which no great effusion of blood takes place.’ Today’s anaesthetists are only too familiar with ‘great effusions of blood’ and it is this that has brought nitrous oxide once more under the spotlight, since operations involving heavy blood loss do not usually last less than two hours. Ever since its first (unsuccessful) use as an anaesthetic agent by Horace Wells in 1845, the role of nitrous oxide in contemporary anaesthetic practice has been keenly debated. For further information about the history of nitrous oxide, readers are referred to a seminal series of articles by Smith in the British Journal of Anaesthesia, of which the most recent is referenced [3]. The rest of this editorial will attempt to provide a current review of its place in modern anaesthesia. Nitrous oxide has a minimum alveolar concentration (MAC) of 105% at 1 atm in humans [4] and thus at ambient pressure cannot be used as a single anaesthetic agent. It is most widely used as a carrier gas for other more potent volatile agents, its analgesic properties reducing opioid need in the operative period. In combination with 50% oxygen (as Entonox) it is used extensively in delivery suites around the world for pain relief in labour and by field emergency staff for analgesia, usually for trauma. It has also been used in alcohol dependency withdrawal programmes. The administration of high concentrations of nitrous oxide to patients has caused concern among anaesthetists who worried about the risk of delivering a hypoxic mixture of inspired gas. It was this fear that led to the introduction of mechanisms linking oxygen and nitrous oxide flowmeters such that a hypoxic mixture could not be delivered. Should another gas be deemed suitable to replace nitrous oxide in the future then the technology for hypoxic mixture prevention will already be in place. Up until recently there has not been a rapidly acting opioid that could provide the same degree of analgesia as nitrous oxide, whose action would also terminate as quickly as that of the gas. The arrival of remifentanil means that this is now no longer the case and may stimulate some commentators to suggest that nitrous oxide can no longer justify its place in the anaesthetic armoury. The cost issue will no doubt be raised by those responsible for budgets; this debate surrounds any new anaesthetic technique and will thus not be discussed further here. The kinetics of nitrous oxide have intrigued investigators ever since its discovery, although only in the last 50 years have we understood how the gas washes in and out of the body. Stenqvist [5] provides a useful review for those wishing to read more about this topic. The relative insolubility of nitrous oxide has aroused most interest since it is this aspect of the gas that has led to much of the criticism associated with it. It increases the size of pneumothoraces and air emboli, it increases middle ear pressure and causes bowel distention, both of which may be associated with postoperative nausea and vomiting. It has been known that its presence can cause postoperative hypoxaemia since Fink described the phenomenon of diffusion anoxia in 1955 [6], but whether or not this is important clinically has been contested in the literature [7, 8]. Since the incidence of hypoxaemia in the immediate postoperative period can be significantly reduced by the administration of supplemental oxygen this point remains largely of academic interest. What is certain is that diffusion hypoxia can only occur if there is present in sufficient quantities a gas that is less soluble in blood than air. The most convincing evidence that nitrous oxide may be detrimental to those to whom it is administered has been gathered by investigators concerned with the effects of the gas on bone marrow. In 1978, Amess and coworkers demonstrated that exposure for 24 h to nitrous oxide interfered with synthesis of DNA [9]. This confirmed the earlier work of Banks et al. [10] who showed that nitrous oxide converts the cobalt in vitamin B12 from the monovalent form to the bivalent form and thus inactivates it. This leads to the megaloblastic changes seen in individuals exposed to nitrous oxide for long periods and Nunn [11] has suggested that it is probably also responsible for the fetotoxicity attributable to nitrous oxide. It is well documented that prolonged exposure to nitrous oxide can lead to subacute combined degeneration of the spinal cord, but there has recently been a report of a patient who developed this condition after a single exposure lasting 8 h [12]. Interference with DNA synthesis may be detected by demonstrating an abnormal result from a deoxyuridine (dU) suppression test and abnormal tests have been reported in patients exposed to nitrous oxide for as little as 2–4 h [13, 14]. Amos and colleagues [15] raised the possibility that compromised patients may be more susceptible to the effects of nitrous oxide, by reporting a series of patients requiring intensive care in which 18 out of 22 who developed megaloblastic Anaesthesia, 1998, 53, pages 213–215 ................................................................................................................................................................................................................................................

Comparison of intramuscular ketorolac and morphine in pain control after laparotomy

Ketorolac, a prostaglandin synthetase‐inhibiting analgesic, was compared with morphine for relief of pain after laparotomy for gynaecological surgery. Eighty patients were studied; they were given either ketorolac 30 mg intramuscularly followed by 10 mg 4‐hourly as required, or morphine 10 mg intramuscularly 4‐hourly as required, administered in a double‐blind, randomised fashion. Pain scores (verbal and visual analogue) were recorded at baseline and assessed at 30 and 60 minutes and then hourly for 6 hours. Pain relief was measured at the same times. Pain and pain‐relief scores were further assessed on the evening of day 1 and at 24 hours. Pain scores were similar in the two groups but pain‐relief scores were better in the morphine group. A considerable number of patients suffered postoperative nausea and vomiting but there was no difference between the groups. One patient in the ketorolac group had unexplained hypotension. It is concluded that ketorolac can provide effective postoperative analgesia.

Analgesic effects of sublingual buprenorphine

The analgesic effects of sublingually administered buprenorphine 0.4 mg have been compared with morphine 10 mg given intramuscularly in patients following operation. The results indicate a slower onset of action for buprenorphine but of much longer duration than morphine. There were no serious side effects or difference in their incidence between the two drugs.

Pregnanolone: a new steroid intravenous anaesthetic

The intravenous steroid anaesthetic pregnanolone has been investigated as an induction agent in 60 fit adults premedicated with morphine and atropine. The drug was given in a stepwise fashion starting with 0.5 mg.kg−1; following a successful induction, the next patient received 15% less, while the subsequent patient received 15% more if anaesthesia was not achieved. Taking loss of eyelash reflex as the end point, 31 patients were satisfactorily induced; the AD50 in these patients was 0.44 mg.kg−1 (95% CI 0.41–0.47). A further 23 patients were induced satisfactorily as assessed by cessation of counting. Induction was trouble free with minimal changes in heart rate and arterial blood pressure, a low incidence of apnoea and few involuntary movements; pain on injection was not a feature. Loss of eyelash reflex is not a good end point for assessment of loss of consciousness following pregnanolone.