Local anesthesia blocks the antiemetic action of P6 acupuncture.

The incidence of postoperative illness was monitored for 6 hours in 74 women premedicated with nalbuphine, 10 mg, and undergoing short gynecologic operations of similar duration under methohexitalnitrous oxide-oxygen anesthesia. Each patient received P6 acupuncture for 5 minutes at the time of administration of premedication. In random order the site of the acupuncture had been previously infiltrated with normal saline solution in half of the patients and 1% lidocaine in the remaining patients. Postoperative emetic sequelae occurred significantly more often in those who received lidocaine compared with the group that received saline solution. This demonstrates the ability of a local anesthetic administered at the point of stimulation to block the antiemetic action of P6 acupuncture in a manner similar to that shown by others for analgesia.

Cimetidine and ranitidine increase midazolam bioavailability.

Cimetidine has been shown to inhibit the oxidative metabolism of a variety of low- and high-extraction drugs. Despite the findings of initial investigators, there is evidence that ranitidine may exert similar effects. Eight healthy volunteer subjects took part in a within-subject crossover study. They received midazolam, 15 mg, by mouth after pretreatment with cimetidine, ranitidine, or nothing and midazolam, 10 mg, intravenously on separate occasions. Mean absolute bioavailability of midazolam was increased by more than 30% after cimetidine (P less than 0.01) and 26% after ranitidine (P less than 0.05). The data, which agree with a concurrent clinical study indicating greater hypnotic action of midazolam after ranitidine, indicate that this is not a result of enhanced midazolam absorption and that reduced hepatic clearance is the most likely explanation.

Anterograde amnesic effects of pethidine, hyoscine and diazepam in adults.

1. The intravenous administration of 5 and 10 mg of diazepam caused anterograde amnesia in 50 and 90% of adults, the peak effect occurring in 2-3 min and action persisting for 20-30 minutes.2. Hyoscine (0.4 and 0.6 mg) caused amnesia in 35 and 50% of patients with peak effect not occurring until 50-80 min after injection and action persisting for at least 120 minutes.3. With neither drug was there any relationship between the incidence of amnesia and the degree of drowsiness.4. Amnesia was not observed after saline or after 50 mg pethidine.5. On questioning 6 h after a short operation many patients had no memory of an object which they clearly recognized and described 1 h after surgery.

Midazolam. A review of its pharmacological properties and therapeutic use.

Midazolam is a short-acting water-soluble benzodiazepine (at pH less than 4), a member of a new class of imidazobenzodiazepine derivatives. At physiological pH the drug becomes much more lipid soluble. Water solubility minimises pain on injection and venous thrombosis compared with diazepam administered in organic solvent. Midazolam is a hypnotic-sedative drug with anxiolytic and marked amnestic properties. To date it has been used mostly by the intravenous route, for sedation in dentistry and endoscopic procedures and as an adjunct to local anaesthetic techniques. It has proved less reliable than thiopentone, but preferable to diazepam, as an intravenous induction agent and is unlikely to replace the other well established drugs. However, due to the cardiorespiratory stability following its administration, midazolam is useful for anaesthetic induction in poor-risk, elderly and cardiac patients. The short elimination half-life (1.5-3.5h) and the absence of clinically important long acting metabolites make midazolam suitable for long term infusion as a sedative and amnestic for intensive care, but clinical trials have yet to be completed. Thus, a combination of properties make midazolam a useful addition to the benzodiazepine group.

Lorazepam as a sedative-amnesic in an intensive care unit.

A clinical study was carried out to evaluate the usefulness of intravenous lorazepam, given for sedation instead of opiate narcotics or diazepam, in 25 seriously-ill patients being treated in a respiratory and intensive care unit. All but 3 patients were on assisted ventilation. Standard doses of 4 mg lorazepam were given at 4 or 6-hourly intervals for periods up to 25 days. ECG, haemodynamic stability and biological determinations were monitored constantly. Apart from some delay in onset of action, lorazepam proved to be a useful sedative with diminished recall on the part of the patients. No side-effects were reported, nor was there any local reaction to the injection. Cardiac output was measured in 9 patients following intravenous administration of a single-dose of either 4 mg or 8 mg lorazepam. No significant changes were recorded.

Cardiovascular changes during induction of anaesthesia. Influence of three anticholinergic premedicants.

The effects on cardiovascular changes during induction of anaesthesia and intubation of routine premedication with three different anticholinergic drugs, atropine, hyoscine, and glycopyrronium, were compared in a double blind trial. Administration of both atropine and hyoscine, whether intramuscularly or orally, was found to be associated with a high incidence of dysrhythmias. With glycopyrronium the incidence was much lower, but control patients receiving no anticholinergic premedication had no dysrhythmias. The heart rates and blood pressures were similar in all the groups during intubation and cuff inflation. A single dose of suxamethonium was not associated with any bradycardia. The need for routine anticholinergic drug administration should be reconsidered. However, if necessary, glycopyrronium appears to have an obvious advantage over atropine and hyoscine.

Frequency of atopy, allergy, and previous general anaesthesia in surgical specialties.

This paper reports part of a large survey of atopy, allergy, and previous anaesthesia in 10 000 preanaesthetic patients. The occurrence of these risk factors in the various surgical specialties has been assessed. Obstetric patients have a significantly higher frequency of atopy and allergy than the total female population studied. Among males cardiothoracic patients are the only group to have a significantly higher frequency of atopy and allergy than the overall figure for their sex.

Post-thoracotomy pain relief: combined use of cryoprobe and morphine infusion techniques.

In a reported study we found that freezing of the intercostal nerves under direct vision at thoracotomy provided better postoperative analgesia than im morphine on demand. Infusions of morphine were also more effective than when used by the intramuscular route. The benefit on the eighth postoperative day was greatest following the use of the cryoprobe. Further studies were carried out to evaluate the benefit of combining 'cryoprobe' analgesia with infusions of morphine. The combined use of morphine infusion and a cryoprobe did not produce greater postoperative pain relief than the use of the cryoprobe alone with im morphine on demand.

Midazolam for upper gastrointestinal endoscopy.

A water-soluble benzodiazepine, midazolam, was used in 400 patients undergoing upper gastrointestinal endoscopy, alone or in combination with pentazocine and compared with 68 patients given diazepam (Valium). In the last 200 patients the endoscopist used midazolam without the presence of an anaesthetist. The absence of injection pain was the most notable feature of midazolam. The degree of co-operation was similar in all groups but the operating conditions were significantly better when midazolam was combined with pentazocine. There was no significant difference in recovery times between the groups as assessed by the pegboard test. Midazolam is an acceptable alternative to diazepam for upper gastrointestinal endoscopy.

Midazolam sedation for outpatient fibreoptic endoscopy: evaluation of alfentanil supplementation.

Alfentanil, a short-acting opioid, was used as an adjuvant to midazolam for sedation of 30 outpatients undergoing upper gastrointestinal endoscopy. The operating conditions and recovery times were compared with those of a similar group of 30 patients sedated with midazolam only. The use of alfentanil resulted in improved operating conditions and a more rapid recovery. Patient acceptance was high.

Prolongation of the antiemetic action of P6 acupuncture by acupressure in patients having cancer chemotherapy.

Previous work from our department has shown that P6 acupuncture is an effective adjuvant to conventional antiemetic therapy for patients having cytotoxic drugs. However, its efficacy is limited to about 8 h. The current studies show that the application of an elasticized wrist band with a stud placed over the acupuncture point, and pressed regularly every 2 h, will prolong the antiemetic action for 24 h. This proved more effective in hospitalized patients (20/20) than in outpatients (15/20), presumably due to the encouragement given to regularly press the stud. Nausea and vomiting remain problems with cancer chemotherapy despite the use of antiemetics. Following encouraging results with P6 acupuncture (ACP) in postoperative sickness this has been shown to be effective in cancer chemotherapy in 105 patients who, despite the use of conventional antiemetics had been sick following the previous treatment. Electrical stimulation (10 Hz DC) of P6 point for 5 min before administration of the cytotoxic drugs was effective in preventing sickness in 66% and only 6% got no benefit. The ACP was given with the antiemetics which the patients had been receiving. Although there were no side effects with the ACP, the benefit only lasted 6-8 h. This was not important in hospitalized patients where the treatment could be repeated, but was a problem with outpatients. It has been shown that pressure on the P6 point (acupressure) has an antiemetic action. A commercially available elasticized band with a plastic stud (Sea Band) is an effective method of applying pressure to P6 point.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the effects of atropine and glycopyrrolate on various end-organs.

Atropine and glycopyrrolate (glycopyrronium bromide), a quaternary ammonium drug, were evaluated in volunteers following intramuscular administration with respect to effects on various end-organs with cholinergic innervation. Glycopyrrolate appears to be five to six times more potent than atropine in its antisialogogue effect and also exhibits a selective, though prolonged, effect on salivary secretion and sweat gland activity. It has minimal cardiovascular, ocular and central nervous system effects.

Non-invasive stimulation of the P6 (Neiguan) antiemetic acupuncture point in cancer chemotherapy.

The beneficial effects of transcutaneous electrical stimulation of the P6 antiemetic point (Neiguan) as an adjuvant to standard antiemetics was studied in over 100 patients in whom chemotherapy-induced sickness was not adequately controlled by antiemetics alone. Although the results were not quite as good as with invasive acupuncture, more than 75% patients achieved considerable benefit from what was a non-toxic procedure. The use of large diffuse low impedence electrodes simplifies the technique. The 2 hourly application of Sea Bands prolongs the antiemetic action. Best results were obtained from the 2 hourly self-administration of 5 min of transcutaneous electrical stimulation of P6 using a simple battery-operated TENS machine (15 Hz) to activate a large, easy-to-place surface electrode and increasing current until Qi is elicited.

Postoperative gastric emptying in outpatient anesthesia: the effect of opioid supplementation.

Acetaminophen (paracetamol) 20 mg/kg was administered orally to 45 gynecological outpatients who had received either alfentanil 5 micrograms/kg, fentanyl 1 microgram/kg, or no analgesic supplement immediately prior to the induction of general anesthesia. Postoperative gastric emptying, assessed by acetaminophen absorption, was significantly inhibited in those given alfentanil. This inhibition is unlikely to be of great clinical importance and was much less than that found in previous studies using longer-acting opioids such as morphine.

Acupuncture prophylaxis of cancer chemotherapy-induced sickness.

In a multi-facet study we evaluated the efficacy of P6 electroacupuncture (10 Hz applied for 5 min) as an antiemetic in patients receiving a variety of cancer chemotherapy drugs. The study involved 130 (15 in an open pilot study, 10 in a randomized placebo controlled crossover study and 105 in a definitive study) patients who had a history of distressing sickness after previous treatment, and who, on the basis of a previous survey, would be expected to have a 96% chance of this with subsequent therapy. Sickness was either completely absent or reduced considerably in 97% of patients and no side effects were encountered. The limited crossover study, using a 'dummy' acupuncture (ACP) point showed that the beneficial effects were limited to the P6 point. Logistic and ethical considerations excluded the possibility of carrying out a larger placebo-controlled study. While in our hands P6 ACP was an effective antiemetic in patients having cancer chemotherapy, because of the time involved and the brevity of the action (8 h) an alternative approach to electro-ACP is required before this technique is adopted clinically.

P6 acupressure reduces morning sickness.

A prospective study was designed to test the efficacy of pressure at the P6 (Neiguan) acupuncture point, in preventing morning sickness. Three groups of patients in early pregnancy recorded the severity and frequency of sickness over a period of 4 consecutive days following daily pressure at P6 point, pressure at a point near the right elbow and with no treatment. Troublesome sickness was significantly less in both the genuine (23/119) and dummy (41/112) pressure groups as compared with the control series (67/119). When the data are adversely 'weighted' to compensate for the lower incidence of fully completed returns in the active treatment groups, only the P6 group show a significant reduction in sickness. No side effects occurred in either group and while anticipation of benefit may offer a partial explanation for the findings, pressure at the Neiguan point appears to have a specific therapeutic effect.

Use of auditory evoked responses as a measure of recovery from benzodiazepine sedation.

The amplitude of the P300 component of auditory evoked responses was found to be depressed by benzodiazepine sedation and was subsequently used to monitor the recovery of volunteers sedated with midazolam. The amplitude of the evoked responses was found to be highly correlated with blood midazolam levels but to be no more sensitive than standard psychomotor testing in assessing recovery from sedation.

Prospective study of liver function following repeat halothane and enflurane.

In a prospective study of liver function following repeat anaesthesia, patients who received repeat halothane had a higher frequency of abnormal liver enzyme results than a similar group who received repeat enflurane. Obesity and short intervals between administrations increased the likelihood of abnormal liver enzyme activity in the halothane group. Enflurane would seem to be the volatile agent of choice for repeat anaesthesia in such circumstances.

Biotransformation and toxicity of intravenous anesthetics.

Metabolism is less important than redistribution as a factor influencing recovery from intravenous barbiturates, but it plays a more important part than was once thought. In contrast with inhalational agents the metabolites of intravenous anesthetics are not the cause of their side effects. The recent reports of hypersensitivity reactions are serious; they show reactions which could be attributable to histamine release and the histaminoid response may be accompanied by bronchospasm. A retrospective analysis of 70 patients suggests that they are more likely to occur in patients with a history of allergy or drug sensitivity or the prior administration of the same drug. The situation is particularly serious in the case of Althesin but it can occur with all drugs.

The amnesic action of diazepam, flunitrazepam and lorazepam in man.

Studies in man show that it is possible to reliably study the incidence, degree and duration of amnesia produced by drugs by showing patients 10 postcards and testing their ability to recall or recognise them six hours later. Using this method of study it was found that 1 mg flunitrazepam produced a comparable degree of amnesia to 10 mg diazepam, although its action was slightly longer. This difference was more marked when double doses were studied. The onset of the amnesic action of both drugs occurred within 2 minutes of their intravenous injection and rarely persisted for more than 10-15 minutes. In contrast, with 4 mg lorazepam the onset of amnesia was slower and persisted for up to 270 minutes. This was accompanied by a moderate but not excessive amount of drowsiness. Possible clinical uses for such a drug deserve serious consideration.