Ross MacPherson

The pharmacological basis of contemporary pain management.

Pain management has become an increasingly well researched area in medicine over recent years, and there have been advances in a number of areas. While opioids remain an integral part of pain-management strategies, there is now an emphasis on the use of adjuvant drugs, such as paracetamol and anti-inflammatory agents, which through physiological or pharmacological synergism, both enhance pain control and reduce opioid use. The management of neuropathic pain continues to be a challenge. Anti-epileptics and antidepressants, together with clonidine and ketamine, provide the foundations for treatment. Another area of interest has been the widespread use of patient-controlled analgesia and the administration of some drugs, especially opioids, by means other than traditional oral and parenteral routes. The number of new drugs that have reached the stage of clinical trials has been small, yet they offer exciting possibilities. The epibatidine analogue ABT-594 and zinconitide both offer novel approaches to the management of neuropathic pain states, while selective cyclo-oxygenase-2 inhibitors and nitroaspirins may see advances in the management of nociceptive pain states.

Neuropsychological and mood effects of ketamine in electroconvulsive therapy: a randomised controlled trial.

BACKGROUNDnPreliminary evidence suggests that the use of ketamine during electroconvulsive therapy (ECT) may be neuroprotective against cognitive impairment and have synergistic antidepressant effects. This study tested whether the addition of ketamine reduced cognitive impairment and enhanced efficacy over a course of ECT, in a randomised, placebo-controlled, double-blind study.nnnMETHODSnFifty-one depressed patients treated with ultrabrief pulse-width right unilateral ECT were randomised to receive either ketamine (0.5mg/kg) or placebo (saline) in addition to thiopentone during anaesthesia for ECT. Neuropsychological outcomes (measured before ECT, after six treatments, and after the final ECT treatment) and mood outcomes (measured before ECT, and weekly after every three ECT treatments) were measured by a rater blinded to treatment condition.nnnRESULTSnNeuropsychological outcomes did not differ between groups. The ECT-ketamine group had a slightly greater improvement in depressive symptoms over the first week of treatment and at one-week follow up, though there was no overall difference in efficacy at the end of the ECT course. No psychomimetic effects were detected.nnnLIMITATIONSnThe study was conducted in a clinical setting, so not all aspects of ECT treatment were fully controlled. Thiopentone doses differed slightly between groups, in order to accommodate the addition of ketamine to the anaesthetic.nnnCONCLUSIONSnThe addition of ketamine did not decrease cognitive impairment in patients having ultrabrief pulse-width right unilateral ECT, but was safe and slightly improved efficacy in the first week of treatment and at one-week follow up.nnnCLINICAL TRIALS REGISTRATIONnClinicaltrials.gov ID: NCT00680433. Ketamine as an anaesthetic agent in electroconvulsive therapy (ECT). www.clinicaltrials.gov.

Augmentation Strategies in Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is a highly effective treatment, but strategies to enhance therapeutic outcomes are occasionally needed. This review examines the evidence for approaches used for enhancing seizure production: hyperventilation, pretreatment with xanthines, and use of remifentanil or ketamine in ECT anesthesia. Hyperventilation may be a useful strategy to enhance seizure production, but its effects on ECT outcomes have not been systematically studied and require further research. Pretreatment with caffeine, theophylline or aminophylline (xanthines) prolongs the duration of ECT seizures but has not been clearly shown in controlled trials to increase efficacy. Caution is also warranted because their use may be associated with significant adverse effects. There are case reports of the usefulness of remifentanil in assisting seizure induction by reducing the dose of barbiturate anesthetic required, but there are no controlled data on whether it independently enhances efficacy outcomes. Preliminary evidence suggests that ketamine and ECT may have synergistic antidepressant effects, although this needs to be further examined in randomized controlled trials.

Cognitive impairment following electroconvulsive therapy--does the choice of anesthetic agent make a difference?

The range of drugs available to provide anesthesia for patients undergoing electroconvulsive therapy (ECT) is ever increasing. Initially, anesthetic agents were selected on the basis of their capacity not to antagonize the induced seizure. This was not always a simple task because almost all general anesthetic agents have in built antiepileptic activity. Nonbarbiturate agents such as propofol have been successfully used as alternatives to thiopental and methohexitone, but this drug too has antiepileptic properties. Most recently, opioid-like drugs such as remifentanil have been used, and there has been renewed interest in ketamine, a phencyclidine derivative. Attention has also focused on whether the anesthetic agent selected may affect the cognitive impairment seen after ECT. Studies in this area are limited, but early results suggest that agents such as ketamine may have particular benefit. This article reviews the current literature dealing with anesthesia and postoperative cognitive impairment in general and with regard to ECT in particular.

The effect of electrode placement and pulsewidth on asystole and bradycardia during the electroconvulsive therapy stimulus

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, and different forms are increasingly used in clinical practice. This study investigated the acute cardiac effects of different forms of ECT: bitemporal and bifrontal (1.5 times seizure threshold), and right unilateral (RUL) (five times seizure threshold). For RUL ECT, the effect of stimulus pulsewidth (1.0 or 0.3 ms) was also examined. Electrocardiograms recorded just prior to and during the ECT stimulus in 476 ECT treatments in 114 patients were examined. The degree of bradycardia (any slowing of heart rate) and incidence of asystole (absence of heart beats for ≥5 s) during the ECT stimulus were measured from these traces. Regression analyses estimated the contribution of patient and ECT treatment factors to the risk of bradycardia and asystole. Bifrontal ECT was associated with less severe bradycardia than bitemporal or RUL ECT (p<0.001). Modelling showed, for a mean pre-ECT heart rate of 85 beats per minute (bpm), expected heart rates during the stimulus were 78 bpm (bifrontal), 46 bpm (bitemporal) and 35 bpm (RUL). Bifrontal ECT was also associated with a lower incidence of asystole than RUL ECT (corrected odds ratio 1:207) and bitemporal ECT (corrected odds ratio 1:24). Ultrabrief pulsewidth stimulation resulted in lesser bradycardia and asystole than standard pulsewidth stimulation for RUL ECT. Modelling showed, for a mean pre-ECT heart rate of 86 bpm, expected heart rates were 43 bpm (ultrabrief RUL) and 26 bpm (RUL). Bradycardia and asystole were relatively common side-effects during the ECT stimulus. Bifrontal ECT was associated with the lowest risk of bradycardia and asystole during ECT and should be considered for patients at risk of arrhythmias and prolonged asystole during ECT.

Effective strategy to guide pathology test ordering in surgical patients

Background:u2003 Ordering of pathology testing by junior medical staff is often a haphazard process with little regard to the appropriateness of test ordering. The aim of the present study was to reduce ordering of inappropriate pathology tests in surgical patients attending the pre‐admission clinic (PAC) through the introduction of a protocol‐based test ordering system and to create an environment where such improvement can be sustained.

Does remifentanil improve ECT seizure quality

Studies have reported that co-adjuvant remifentanil can enhance electroconvulsive therapy (ECT) seizure quality, putatively by allowing a reduction in the dosage of the main anaesthetic agents, as the latter have anticonvulsant properties. However, whether remifentanil also has direct effects on ECT seizure quality, and by implication, treatment efficacy, is unknown. This is the first study examining the effect of adjuvant remifentanil on ECT seizure quality when the dose of conventional anaesthesia remained unchanged. A total of 96 ECT sessions (from 36 patients) were retrospectively analysed. Subjects received ECT with and without remifentanil (1xa0µg/kg), while the dose of thiopentone (3–5xa0mg/kg) or propofol (1–2xa0mg/kg) was unchanged. Seizure quality indices (time to slow wave activity or TSLOW, amplitude, regularity, stereotypy, post-ictal suppression) and duration were assessed through a structured rating scale by a single trained blinded rater. Linear mixed-effects models with random subject effects analysed the effect of remifentanil on seizure parameters, controlling for other variables that can affect seizure quality or duration. Remifentanil was given in 47.9xa0% of the ECT sessions. Co-adjuvant remifentanil had no effects on any of the seizure quality parameters analysed [TSLOW (Exa0=xa0−0.21, pxa0>xa00.1), amplitude (Exa0=xa00.08, pxa0>xa00.5), regularity (Exa0=xa0−0.05, pxa0>xa00.5), stereotypy (Exa0=xa0−0.02, pxa0>xa00.5), suppression (Exa0=xa0−0.3, pxa0>xa00.05)] or on seizure duration (Exa0=xa0−0.25, pxa0>xa00.1). While adjuvant remifentanil may be a useful strategy for reducing anaesthetic dosage in ECT, present evidence suggests that remifentanil does not have intrinsic properties that enhance ECT seizures.

Low dose lignocaine added to propofol does not attenuate the response to electroconvulsive therapy

BACKGROUNDnThe addition of small amounts of lignocaine (50 mg) to propofol (200 mg) has been previously shown to reduce pain in injection, a common problem with this particular anaesthetic agent. The aim of this study was to investigate whether using the mixture of propofol plus lignocaine had any adverse effects on ECT seizure expression (duration, and ictal quality).nnnMETHODnIctal EEG records were retrospectively examined in 29 patients who underwent 80 pairs of ECT treatments, one given with propofol alone and one with propofol plus lignocaine. Ictal quality was manually rated for the transition from the polyspike phase to the slow wave phase, amplitude of the mid-ictal spike-and-wave phase, regularity of morphology of the predominant pattern of the slow wave phase, stereotypy, variability of the morphology and amplitude of the slow wave phase and post-ictal suppression.nnnRESULTSnThere was no significant difference in seizure duration between the two groups (33.4+/-13.0 s (propofol) vs. 33.6+/-11.2 s (propofol plus lignocaine). Furthermore although the addition of lignocaine delayed the onset of the slow wave phase by about 1s, it resulted in an improvement in three of four of the other measures of ictal quality.nnnCONCLUSIONnThe addition of a small dose of lignocaine to propofol during ECT treatment enhanced rather than reduced the quality of the seizures produced.

Extemporaneous prescribing: whatever happened to it? A survey of Australian general practitioners

Objectives: Recent Australian and New Zealand studies have shown that dispensing of extemporaneous products by pharmacists has declined over recent years to only 1 to 2% of total prescriptions. The purpose of this study was to survey general practitioners (GPs) to identify the scope of extemporaneous prescribing, reasons for any limitations to such prescribing and their interest in further education.

Implementing a Pharmacist Charting Service in the Pre- Admission Clinic

To implement a pharmacist charting service in the preadmission clinic (PAC) and describe a preparatory process for the initiation of this service.