Showing papers in "BJA: British Journal of Anaesthesia in 1999"

Near infrared spectroscopy.

Abstract: Near infrared spectroscopy (NIRS) is an imaging technique used in both clinical and emergency medicine, as well as in research laboratories to quantify and measure the oxygenation status of human tissue non-invasively. This is done by monitoring in vivo changes of the oxygen saturation of hemoglobin molecules in the body, based on the absorbance of near-infrared light by hemoglobin. With regards to NIRS in human tissue, this chapter will primarily be concerned with discerning the oxygenation status of cerebral tissue. The importance of such a measure, especially in cerebral physiology, is that the human brain utilizes oxygen to continuously supply neurons with energy used for vital body functioning. In the absence of oxygen, as is the case during ischemic stroke or desanguination, cognitive and functional impairment resulting in death often occurs. NIRS technology makes it possible to apply critical safety thresholds with regards to cerebral tissue saturation in order to avoid dangerously low levels with the primary goal being to reduce mortality rates and cognitive deficits due to cerebral hypoxemia.

Magnesium: physiology and pharmacology.

Abstract: Magnesium has an established role in obstetrics and an evolving role in other clinical areas, in particular cardiology. Many of the effects involving magnesium are still a matter of controversy. Over the next decade, it is likely that improvements in the measurement of magnesium, a clearer understanding of the mechanisms of its actions and further results of clinical studies will help to elucidate its role, both in terms of treating deficiency and as a pharmacological agent.

Comparison of four methods for assessing airway sealing pressure with the laryngeal mask airway in adult patients.

Abstract: We have compared four tests for assessing airway sealing pressure with the laryngeal mask airway (LMA) to test the hypothesis that airway sealing pressure and inter-observer reliability differ between tests. We studied 80 paralysed, anaesthetized adult patients. Four different airway sealing pressure tests were performed in random order on each patient by two observers blinded to each other’s measurements: test 1 involved detection of an audible noise; test 2 was detection of end-tidal carbon dioxide in the oral cavity; test 3 was observation of the aneroid manometer dial as the pressure increased to note the airway pressure at which the dial reached stability; and test 4 was detection of an audible noise by neck auscultation. Mean airway sealing pressure ranged from 19.5 to 21.3 cm H2O and intra-class correlation coefficient was 0.95-0.99. Inter-observer reliability of all tests was classed as excellent. The manometric stability test had a higher mean airway sealing pressure (P

A prospective, randomized comparison of preoperative and continuous balanced epidural or paravertebral bupivacaine on post-thoracotomy pain, pulmonary function and stress responses.

Abstract: Both epidural and paravertebral blocks are effective in controlling post-thoracotomy pain, but comparison of preoperative and balanced techniques, measuring pulmonary function and stress responses, has not been undertaken previously. We studied 100 adult patients, premedicated with morphine and diclofenac, allocated randomly to receive thoracic epidural bupivacaine or thoracic paravertebral bupivacaine as preoperative bolus doses followed by continuous infusions. All patients also received diclofenac and patient-controlled morphine. Significantly lower visual analogue pain scores at rest and on coughing were found in the paravertebral group and patient-controlled morphine requirements were less. Pulmonary function was significantly better preserved in the paravertebral group who had higher oxygen saturations and less postoperative respiratory morbidity. There was a significant increase in plasma concentrations of cortisol from baseline in both the epidural and paravertebral groups and in plasma glucose concentrations in the epidural group, but no significant change from baseline in plasma glucose in the paravertebral group. Areas under the plasma concentration vs time curves for cortisol and glucose were significantly lower in the paravertebral groups. Side effects, especially nausea, vomiting and hypotension, were troublesome only in the epidural group. We conclude that with these regimens, paravertebral block was superior to epidural bupivacaine.

'Alveolar recruitment strategy' improves arterial oxygenation during general anaesthesia.

Abstract: Abnormalities in gas exchange during general anaesthesia are caused partly by atelectasis. Inspiratory pressures of approximately 40 cm H2O are required to fully re-expand healthy but collapsed alveoli. However, without PEEP these re-expanded alveoli tend to collapse again. We hypothesized that an initial increase in pressure would open collapsed alveoli; if this inspiratory recruitment is combined with sufficient end-expiratory pressure, alveoli will remain open during general anaesthesia. We tested the effect of an 'alveolar recruitment strategy' on arterial oxygenation and lung mechanics in a prospective, controlled study of 30 ASA II or III patients aged more than 60 yr allocated to one of three groups. Group ZEEP received no PEEP. The second group received an initial control period without PEEP, and then PEEP 5 cm H2O was applied. The third group received an increase in PEEP and tidal volumes until a PEEP of 15 cm H2O and a tidal volume of 18 ml kg-1 or a peak inspiratory pressure of 40 cm H2O was reached. PEEP 5 cm H2O was then maintained. There was a significant increase in median PaO2 values obtained at baseline (20.4 kPa) and those obtained after the recruitment manoeuvre (24.4 kPa) at 40 min. This latter value was also significantly higher than PaO2 measured in the PEEP (16.2 kPa) and ZEEP (18.7 kPa) groups. Application of PEEP also had a significant effect on oxygenation; no such intra-group difference was observed in the ZEEP group. No complications occurred. We conclude that during general anaesthesia, the alveolar recruitment strategy was an efficient way to improve arterial oxygenation.

The sitting position in neurosurgery: a critical appraisal.

Abstract: The potential for serious complications after venous air embolism and successful malpractice liability claims are the principle reasons for the dramatic decline in the use of the sitting position in neurosurgical practice. Although there have been several studies substantiating the relative safety compared with the prone or park bench positions, its use will continue to decline as neurosurgeons abandon its application and trainees in neurosurgery are not exposed to its relative merits. How can individual surgeons continue to use this position? Will individual, difficult surgical access cases be denied the obvious technical advantages of the sitting position? Limited use of the sitting position should remain in the neurosurgeon's armamentarium. However, several caveats must be emphasized. Assessment of the relative risk-benefit, based on the individual patient's physical status and surgical implications for the particular intracranial pathology, is of paramount importance. The patient should be informed of the specific risks of venous air embolism, quadriparesis and peripheral nerve palsies. Appropriate charting of patient information provided and special consent issues are essential. An anaesthetic input into the decision to use the sitting position is a sine qua non. The presence of a patient foramen ovale is an absolute contraindication. Preoperative contrast echocardiography should be used as a screening technique to detect the population at risk of paradoxical air embolism caused by the presence of a patent foramen ovale. The technique involves i.v. injection of saline agitated with air and a Valsalva manoeuvre is applied and released. Use of this position necessitates supplementary monitoring to promptly detect and treat venous air embolism. Doppler ultrasonography is the most sensitive of the generally available monitors to detect intracardiac air. The use of a central venous catheter is recommended, with the tip positioned close to the superior vena cava junction with the right atrium, to aspirate intravascular gas. Measures to minimize hypotension associated with the sitting position include a slow, staged positioning over 5-10 min and use of the 'G suit' inflated with compressed air applied to the lower extremities and pelvis. Use of the sitting or upright position for patients undergoing posterior fossa and cervical spine surgery presents unique challenges for the anaesthetist. With appropriate patient selection and preparation, and using prudent intraoperative monitoring and anaesthetic techniques, selected patients should still benefit from the optimum access to mid-line lesions, improved cerebral venous decompression, lower intracranial pressure and enhanced gravity drainage of blood and CSF associated with the sitting position.

Metoclopramide in the prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized, placebo-controlled studies.

Abstract: Metoclopramide has been used for almost 40 yr to prevent postoperative nausea and vomiting (PONV) We have reviewed the efficacy and safety of metoclopramide for the prevention of PONV A systematic search (MEDLINE, EMBASE, manufacturers' databases, hand searching, bibliographies, all languages, up to June 1998) was performed for full reports of randomized comparisons of metoclopramide with placebo in surgical patients Relevant end-points were prevention of early PONV (within 6 h after operation), late PONV (48 h) and adverse effects Combined data were analysed using relative benefit/risk and number-needed-to-treat/harm In 66 studies, 3260 patients received 18 different regimens of metoclopramide, and 3006 controls received placebo or no treatment There was no evidence of dose-responsiveness with oral, im, intranasal or iv metoclopramide in children and adults In adults, the best documented regimen was 10 mg iv There was no significant anti-nausea effect The numbers-needed-to-treat to prevent early and late vomiting were 91 (95% confidence intervals 55-27) and 10 (6-41), respectively In children, the best documented regimen was 025 mg kg-1 iv The number-needed-to-treat to prevent early vomiting was 58 (39-11) There was no significant late anti-vomiting effect Minor drug-related adverse effects (sedation, dizziness, drowsiness) were not significantly associated with metoclopramide There was one adult who experienced extrapyramidal symptoms with metoclopramide

Relative potencies of bupivacaine and ropivacaine for analgesia in labour.

Abstract: We have used the technique of randomized, double-blind sequential allocation to compare the minimum local analgesic concentrations (MLAC) of epidural bupivacaine and ropivacaine for women in the first stage of labour. The test bolus was 20 ml of local anaesthetic solution. The concentration was determined by the response of the previous woman to a higher or lower concentration of local anaesthetic, according to up-down sequential allocation. Efficacy was assessed using a 100-mm visual analogue pain score (VAPS). The test solution had to achieve a VAPS of 10 mm or less to be judged effective. For bupivacaine, MLAC was 0.093 (95% CI 0.076-0.110)% w/v, and for ropivacaine, 0.156 (95% CI 0.136-0.176)%w/v (P

Pulmonary aspiration of gastric contents in anaesthesia.

Abstract: Pulmonary aspiration of gastric contents is one of the most feared complications of anaesthesia. Prevention of aspiration by identification of patients at risk, preoperative fasting, drug treatment and various anaesthetic manoeuvres are cornerstones of safe anaesthetic practice. Not surprisingly, the number of articles and case reports regarding the pulmonary consequences of gastric aspiration is vast and recommendations are often conflicting. We consider briefly the pathophysiology of this condition and examine the evidence regarding incidence, morbidity and mortality, and possible treatment options. In particular, we will consider if our fear of aspiration is exaggerated and what evidence supports the routine use of pharmacological agents to decrease gastric acidity and volume.

Nitrous oxide does not alter bispectral index: study with nitrous oxide as sole agent and as an adjunct to i.v. anaesthesia.

Abstract: We have studied the effect of nitrous oxide on bispectral index (BIS), calculated from a bipolar encephalogram. Inhalation of 70% nitrous oxide resulted in loss of consciousness in all healthy volunteers (n = 10) but no change in BIS. Brief inhalation up to 1.2% sevoflurane also resulted in loss of consciousness in volunteers (n = 5), but with sevoflurane, BIS decreased. BIS and the haemodynamic effects of adding nitrous oxide were also measured during coronary artery bypass surgery in patients (n = 10) receiving midazolam and fentanyl infusions. Measurements were made after 0%, 33%, 66% and 0% nitrous oxide, just before skin incision and after sternotomy. Nitrous oxide caused no change in BIS. BIS may indicate a sufficient hypnotic depth to prevent awareness during surgery, but our study demonstrated that pharmacological unconsciousness-hypnosis can also be reached by mechanisms to which BIS is not sensitive. Thus BIS is a sufficient but not a necessary criterion for adequate depth of anaesthesia or prevention of awareness.

Pulse oximetry plethysmographic waveform during changes in blood volume.

Abstract: Systolic pressure variation (SPV) and its dDown component have been shown to be sensitive factors in estimating intravascular volume in patients undergoing mechanical ventilation. In this study, ventilation-induced changes in pulse oximeter plethysmographic waveform were evaluated after removal and after reinfusion of 10% estimated blood volume. The plethysmographic waveform variation (SPVplet) was measured as the difference between maximal and minimal peaks of waveform during the ventilatory cycle, and expressed as a percentage of the signal amplitude during apnoea. dUp(plet) and dDown(plet) were measured as the distance between the apnoeic plateau and the maximal or minimal plethysmographic systolic waveform, respectively. Intravascular volume was changed by removal of 10% of estimated blood volume and followed by equal volume replacement with Haemaccel. A 10% decrease in blood volume increased SPVplet from mean 17.0 (SD 11.8)% to 31.6 (28.0)% (P = 0.005) and dDown(plet) from 8.7 (5.1)% to 20.5 (12.9)% (P = 0.0005) compared with baseline. Changes in plethysmographic waveform correlated with changes in arterial SPV and dDown (r = 0.85; P = 0.0009). In the absence of invasive arterial pressure monitoring, ventilation-induced waveform variability of the plethysmographic signal measured from pulse oximetry is a useful tool in the detection of mild hypovolaemia.

Dynamics of re-expansion of atelectasis during general anaesthesia

Abstract: A major cause of impaired gas exchange during general anaesthesia is atelectasis, causing pulmonary shunt. A 'vital capacity' (VC) manoeuvre (i.e. inflation of the lungs up to 40 cm H2O, maintained for 15 s) may re-expand atelectasis and improve oxygenation. However, such a manoeuvre may cause adverse cardiovascular effects. Reducing the time of maximal inflation may improve the margin of safety. The aim of this study was to analyse the change over time in the amount of atelectasis during a VC manoeuvre in 12 anaesthetized adults with healthy lungs. I.v. anaesthesia with controlled mechanical ventilation (VT 9 (SD 1) ml kg-1) was used. For the VC manoeuvre, the lungs were inflated up to an airway pressure (Paw) of 40 cm H2O. This pressure was maintained for 26 s. Atelectasis was assessed by analysis of computed x-ray tomography. The amount of atelectasis, measured at the base of the lungs, was 4.0 (SD 2.7) cm2 after induction of anaesthesia. The decrease in the amount of atelectasis over time during the VC manoeuvre was described by a negative exponential function with a time constant of 2.6 s. At an inspired oxygen concentration of 40%, PaO2 increased from 17.2 (4.0) kPa before to 22.2 (6.0) kPa (P = 0.013) after the VC manoeuvre. Thus in anaesthetized adults undergoing mechanical ventilation with healthy lungs, inflation of the lungs to a Paw of 40 cm H2O, maintained for 7-8 s only, may re-expand all previously collapsed lung tissue, as detected by lung computed tomography, and improve oxygenation. We conclude that the previously proposed time for a VC manoeuvre may be halved in such subjects.

Postoperative nausea and vomiting in paediatric patients.

Abstract: The past decade has witnessed the introduction of several significant innovations to combat POV, particularly the introduction of serotonin antagonists and the use of combinations of drugs for analgesia and control of POV. Based on current knowledge, the anaesthetic plan for a patient with a previous history of severe PONV and undergoing a procedure known to be associated with a high incidence of this problem should include premedication with a benzodiazepine and/or clonidine and the preferential use of regional anaesthetic techniques. If general anaesthesia is essential, anaesthetists should consider the use of propofol for both induction and maintenance of anaesthesia, together with avoidance of nitrous oxide, opioids and neuromuscular antagonists. Pain control is extremely important, and a peripheral regional block should be used if possible. A combination of prophylactic antiemetics such as dexamethasone, a 5-HT3 antagonist and an antiemetic of a different class (e.g. perphenazine or dimenhydrinate) should be administered. Non-pharmacological measures such as acupressure and suggestion should also be considered, together with nursing measures to avoid sudden movement from one position to another during the postoperative period. A quiet environment, adequate i.v. fluids and not forcing the patient to drink before discharge all contribute to decreased emesis. It is possible that the advent of a new class of antiemetic agents, the NKI antagonists, may have major effects on the incidence of this complication. Drugs in this group differ from other currently available drugs in having the ability to effectively block the emetic response to many stimuli in experimental animals. Postoperative vomiting remains a significant problem, resulting in patient suffering and prolonged recovery from anaesthesia. Our aim should be to eliminate this complication in all children who require surgery. It should not be considered merely as the 'big, little problem'.

Continuous cardiac output measurement: pulse contour analysis vs thermodilution technique in cardiac surgical patients.

Abstract: We have analysed the clinical agreement between two methods of continuous cardiac output measurement pulse contour analysis (PCCO) and a continuous thermodilution technique (CCO), were both compared with the intermittent bolus thermodilution technique (BCO). Measurements were performed in 26 cardiac surgical patients (groups 1 and 2, 13 patients each, with an ejection fraction > 45% and < 45%, respectively) at 12 selected times. During operation, mean differences (bias) between PCCO-BCO and CCO-BCO did not differ in either group. However, phenylephrine-induced increases in systemic vascular resistance (SVR) by approximately 60% resulted in significant differences. Significantly higher absolute bias values of PCCO-BCO compared with CCO-BCO were also found early after operation in the ICU. Thus PCCO and CCO provided comparable measurements during coronary bypass surgery. After marked changes in SVR, further calibration of the PCCO device is necessary.

Adverse effects of cannabis and cannabinoids.

Abstract: The use of cannabis for both recreational and medicinal purposes dates back for thousands of years.15 91 It is perceived widely by recreational users as a harmless drug, a view fostered by some sections of the press and even (surprisingly) by a leading medical journal.73 The opinions of 74% of doctors in a British Medical Association survey92 and of a Select Committee of the House of Lords59 that cannabis should again be available on prescription (as it was until 1971) appear to support this belief. Therapeutic uses of cannabis have recently been reviewed by the British Medical Association17 which concluded that herbal cannabis is unsuitable for medical use. Nevertheless, it was recommended that research on the value of individual pure cannabinoids in a variety of conditions, including multiple sclerosis, spinal cord injury, chronic pain and palliative care, should be encouraged. Synthetic cannabinoids such as nabilone (in the UK) and dronabinol (in the USA) already have an established use as antiemetics in nausea and vomiting associated with cancer chemotherapy. However, no drug is without unwanted effects. It is timely to review the adverse effects of cannabis, especially in view of the increased prevalence of its recreational use in the UK, increased potency of modern preparations and present interest in the therapeutic possibilities of cannabinoids. This review is based on a Medline search of articles on the pharmacology and effects of cannabis and cannabinoids 1980–1998, supplemented by comprehensive books and compendia, and standard books and articles from the older literature. Relevant books and articles were hand-searched for additional references. The search was conducted originally for reports commissioned by the Department of Health,7 the British Medical Association17 and the Ministry of Defence (unpublished), but has since been updated. The articles quoted in this review were selected from a very large bibliography as having relevance to the recreational use of cannabis and the medical use of cannabinoids in the UK today. Constraints on the number of references permitted meant further selection of original data, but most important

Use of tranexamic acid for an effective blood conservation strategy after total knee arthroplasty.

Abstract: We have investigated the effect of treatment with tranexamic acid, an inhibitor of fibrinolysis, on blood loss, blood transfusion requirements and blood coagulation in a randomized, double-blind, placebo-controlled study of 42 patients after total knee arthroplasty. Tranexamic acid 15 mg kg-1 (n = 21) or an equivalent volume of normal saline (n = 21) was given 30 min before surgery and subsequently every 8 h for 3 days. Coagulation and fibrinolysis values, blood loss and blood units administered were measured before administration of tranexamic acid, 8 h after the end of surgery and at 24 and 72 h after operation. Coagulation profile was examined (bleeding time, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), plasminogen, beta-thromboglobulin and fibrinogen). Fibrinolysis was evaluated by measurement of concentrations of D-dimer and fibrinogen degradation products (FDP). Total blood loss in the tranexamic acid group was 678 (SD 352) ml compared with 1419 (607) ml in the control group (P

Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 1: Pharmacodynamic and pharmacokinetic interactions.

Abstract: Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with anaesthetic-sparing effects. We have determined the pharmacodynamic and pharmacokinetic interactions between dexmedetomidine and isoflurane in volunteers. Nine male subjects were allocated randomly to receive isoflurane anaesthesia preceded by infusion of dexmedetomidine on three separate occasions, 2 weeks apart. Dexmedetomidine target plasma concentrations were 0.0 (placebo), 0.3 ng ml-1 (low-dex) and 0.6 ng ml-1 (high-dex). End-tidal isoflurane concentrations at which gross purposeful movement and response to verbal commands occurred were identified. In the recovery period, sedation scores and digit symbol substitution tests were recorded. Venous blood samples were obtained before, during and after anaesthesia at predetermined intervals for measurement of plasma concentrations of dexmedetomidine and calculation of standard pharmacokinetic indices (AUC, Cl, Vss, T1/2 alpha, T1/2 beta). The end-tidal isoflurane concentration at which 50% of subjects first responded to the tetanic stimulus was 1.05% in the placebo group, 0.72% in the low-dex group and 0.52% in the high-dex group. We conclude that dexmedetomidine decreased isoflurane requirements in a dose-dependent manner and reduced heart rate, systolic and diastolic arterial pressures. Sedation and slight impairment of cognitive function persisted for several hours after anaesthesia and the end of infusion of dexmedetomidine. Isoflurane did not appear to influence the pharmacokinetics of dexmedetomidine.

Dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy.

Abstract: We have evaluated the antiemetic effect of i.v. dexamethasone compared with saline in the prevention of nausea and vomiting after laparoscopic cholecystectomy. We studied 90 patients requiring general anaesthesia for laparoscopic cholecystectomy, in a randomized, double-blind, placebo-controlled study. The dexamethasone group (n = 45) received dexamethasone 8 mg i.v. and the saline group received saline 2 ml i.v. at induction of anaesthesia. Anaesthesia was maintained with isoflurane in oxygen. We found that 10% of patients in the dexamethasone group compared with 34% in the saline group reported vomiting (P

Comparison of bispectral index, 95% spectral edge frequency and approximate entropy of the EEG, with changes in heart rate variability during induction of general anaesthesia.

Abstract: We have compared bispectral index (BIS), 95% spectral edge frequency (SEF) and approximate entropy (ApEn) in 37 patients during induction and recovery from a short general anaesthetic. Heart rate variability (HRV) was also compared during induction only. These indices were noted at the start of induction, when a syringe held between the thumb and fingertips was dropped, at insertion of a laryngeal mask or tracheal tube (tube insertion), at incision, at the end of surgery, on return of the gag reflex and when the patient could follow a verbal command. When indices at the start of induction were compared with those at tube insertion, all four decreased significantly. BIS decreased from a mean of 95.38 (SEM 1.02) to 44.22 (1.05), mean SEF from 20.91 (1.19) to 14.14 (0.70) Hz, mean HRV from 37.1 (7.75) to 17.9 (3.6) bpm2 and ApEn from 0.90 (0.06) to 0.65 (0.04). Using logistic regression, the indices were compared both individually and in combination as to the power of distinguishing awake (at pre-induction) from asleep (at tube insertion) states. BIS had the best predictive power, with a sensitivity of 97.3%, specificity 94.4%, positive predictive value 94.7% and negative predictive value 97.1%. A combination of the indices conferred no additional predictive advantage.

Postoperative analgesia with i.v. patient-controlled morphine: effect of adding ketamine.

Abstract: We have studied the effect of adding ketamine to i.v. morphine patient-controlled analgesia (PCA) for the treatment of pain after laparotomy. Thirty patients were allocated randomly to receive PCA with saline or ketamine in a double-blind, randomized study. Analgesia was started in the recovery room when visual analogue scale (VAS) scores were > 4. A bolus dose of morphine 3 mg was given to all the patients followed by i.v. PCA. Simultaneously, an infusion of ketamine 2.5 micrograms kg-1 min-1 or saline was started. Pain scores, morphine consumption and side effects were noted for up to 48 h after the start of PCA. VAS scores decreased significantly with time (P = 0.0001) and were similar (P = 0.3083) in both groups. Cumulative morphine consumption at 48 h was significantly lower in the ketamine group (28 mg) than in the control group (54 mg) (P = 0.0003). Nausea was less frequent in the ketamine group (P = 0.03).

Omitting antagonism of neuromuscular block: effect on postoperative nausea and vomiting and risk of residual paralysis. A systematic review.

Abstract: We have estimated the effect of omitting antagonism of neuromuscular block on postoperative nausea and vomiting. A systematic search (MEDLINE, EMBASE, Biological Abstracts, Cochrane library, reference lists and hand searching; no language restriction, up to March 1998) was performed for relevant randomized controlled trials. In eight studies (1134 patients), antagonism with neostigmine or edrophonium was compared with spontaneous recovery after general anesthesia with pancuronium, vecuronium, mivacurium or tubocurarine. On combining neostigmine data, there was no evidence of an antiemetic effect when it was omitted. However, the highest incidence of emesis with neostigmine 1.5 mg was lower than the lowest incidence of emesis with 2.5 mg. Numbers-needed-to-treat to prevent emesis by omitting neostigmine compared with using it were consistently negative with 1.5 mg, and consistently positive (3-6) with 2.5 mg. There was a lack of evidence for edrophonium. In two studies, three patients with spontaneous recovery after mivacurium or vecuronium needed rescue anticholinesterase drugs because of clinically relevant muscle weakness (number-needed-to-harm, 30). Omitting neostigmine may have a clinically relevant antiemetic effect when high doses are used. Omitting antagonism, however, introduces a non-negligent risk of residual paralysis even with short-acting neuromuscular blocking agents.

Cerebral near infrared spectroscopy: emitter-detector separation must be increased.

Abstract: We have compared the effect of increasing optode separation (range 0.7-5.5 cm) on the sensitivity of near infrared spectroscopy (NIRS) to discrete reductions in scalp and cerebral oxygenation in 10 healthy men (mean age 32, range 26-39 yr) using multichannel NIRS. During cerebral oligaemia (a mean reduction in middle cerebral artery flow velocity of 47%) induced by a mean reduction in end-tidal PCO2 of 2.4 kPa, the decrease in oxyhaemoglobin detected by NIRS became significantly greater with increasing optode separation (P

Closed-loop control of propofol anaesthesia.

Abstract: We describe the use of a closed-loop system to control depth of propofol anaesthesia automatically. We used the auditory evoked potential index (AEPindex) as the input signal of this system to validate it as a true measure of depth of anaesthesia. Auditory evoked potentials were acquired and processed in real time to provide the AEPindex. The AEPindex was used in a proportional integral (PI) controller to determine the target blood concentration of propofol required to induce and maintain general anaesthesia automatically. We studied 100 spontaneously breathing patients. The mean AEPindex before induction of anaesthesia was 73.5 (SD 17.6), during surgical anaesthesia 37.8 (4.5) and at recovery of consciousness 89.7 (17.9). Twenty-two patients required assisted ventilation before incision. After incision, ventilation was assisted in four of these 22 patients for more than 5 min. There was no incidence of intraoperative awareness and all patients were prepared to have the same anaesthetic in future. Movement interfering with surgery was minimal. Cardiovascular stability and overall control of anaesthesia were satisfactory.

Pre-existing medical conditions as predictors of adverse events in day-case surgery.

Abstract: We have developed mathematical models to estimate the risk of perioperative adverse events in patients with pre-existing conditions undergoing day-case surgery. We studied 17,638 consecutive day-case surgical patients in a prospective study. Preoperative, intraoperative and postoperative data were collected. Risk modelling was performed with backward stepwise multiple logistic regression and validated on a separate subset of our patients. Eighteen pre-existing conditions were entered into the model. We adjusted for age, sex, and duration and type of surgery. Seven associations between pre-existing medical conditions and perioperative adverse events were statistically significant. Hypertension predicted the occurrence of any intraoperative event and intraoperative cardiovascular events. Obesity predicted intraoperative and postoperative respiratory events, and smoking and asthma predicted postoperative respiratory events. Gastro-oesophageal reflux predicted intubation-related events. The presented models of risk estimation were validated internally and provided a useful tool for accurate risk estimation.

Inflammation of the rat urinary bladder is associated with a referred thermal hyperalgesia which is nerve growth factor dependent.

Abstract: We have assessed whether a referred somatic hyperalgesia to thermal stimulation of the hind limb of rats occurs after inflammation of the urinary bladder. Furthermore, we evaluated whether any such viscero-somatic hyperalgesia (VSH) is dependent on the neurotrophin nerve growth factor (NGF). Limb withdrawal thresholds from thermal stimulation of both fore and hind limbs were assessed simultaneously at baseline and at fixed times for 24 h after various interventions. After plotting curves for the difference in withdrawal time of fore and hind limbs against time, the area under the curve (AUC) was calculated to provide a single measure over the 24-h period. A negative value indicated relative hyperalgesia of the hind limb. With simple catheterization, although there was a trend towards hind limb hyperalgesia, there was no significant difference in this AUC (mean -100.5) compared with naive control animals (mean AUC +53.6). However, inflammation with 50% turpentine oil was associated with a significant change in AUC (mean -676.8), indicative of relative hyperalgesia of the hind limb. This hyperalgesia was mimicked by intra-vesical instillation of NGF (in place of turpentine) (mean AUC -1418.3 while mean AUC in naive animals was +439.4). Furthermore, prior administration of an NGF sequestering molecule, trkA-IgG, attenuated turpentine-induced VSH. These findings increase our knowledge of the nature of visceral and referred pain and further implicate NGF in the hyperalgesic response to inflammation of the urinary bladder.

A potential mechanism of propofol-induced pain on injection based on studies using nafamostat mesilate.

Abstract: To elucidate the mechanism of propofol-induced pain on injection, we performed several studies using nafamostat mesilate, a kallikrein inhibitor, or lidocaine. As both pretreatment and low-dose mixing with nafamostat produced the same effects on pain reduction, we used the latter method in the following experiments. Low-dose mixing had the same effect on injection pain as mixing with lidocaine. The extent of pain was assessed by measuring bradykinin concentrations by mixing with blood. Propofol and its lipid solvent mixed with blood produced approximately two-fold generation of bradykinin compared with the saline control, and this was inhibited completely by nafamostat and lidocaine. Injection of the lipid solvent before propofol significantly aggravated pain compared with prior injection of saline, although the lipid solvent injected twice caused no change in pain. These results suggest that the lipid solvent for propofol activates the plasma kallikrein-kinin system and produces bradykinin which modifies the injected local vein. This modification of the peripheral vein may increase the contact between the aqueous phase propofol and the free nerve endings of the vessel, resulting in aggravation of propofol-induced pain.

Tissue deposits of hydroxyethyl starch (HES): dose-dependent and time-related.

Abstract: Tissue deposits occur after administration of plasma substitutes. After hydroxyethyl starch (HES), deposits may last for months, causing pruritus and impairment of function. Because elimination of HES deposits has not been demonstrated in humans, we studied 26 patients, for up to 7 yr after HES administration, to assess HES storage. HES dose ranged from 0.34 to 15.00 g kg-1 body weight, and administration intervals from 1 day to 7 yr. Biopsies of the liver, muscle, spleen, intestine or skin were studied using light and electron microscopy and immunohistochemistry. HES storage was dose-dependent, decreased in all organs with time and was greater in patients suffering from pruritus. We conclude that tissue deposition of HES is transitory and dose-dependent, with differences between subjects in severity and duration.

Analgesic efficacy of paracetamol and diclofenac in children receiving PCA morphine.

Abstract: We studied 80 children, aged 5-13 yr, who received PCA with morphine after appendicectomy using a standardized tracheal general anaesthetic. All patients received morphine 0.1 mg kg-1 before surgical incision and all had wound infiltration with bupivacaine 1 mg kg-1 at the end of surgery. Patients were allocated randomly to receive postoperative analgesia with PCA morphine alone, morphine plus diclofenac 1 mg kg-1, morphine plus paracetamol 15-20 mg kg-1 or morphine plus a combination of both diclofenac and paracetamol. Cumulative morphine consumption was significantly reduced by concurrent administration of diclofenac but no additive effect of paracetamol was demonstrable with the doses used in the study. Analgesia, as assessed by movement pain scoring, was significantly improved by the addition of diclofenac despite lower morphine consumption. Adverse effects and duration of PCA were comparable in the four groups.

Antiemetic activity of the NK1 receptor antagonist GR205171 in the treatment of established postoperative nausea and vomiting after major gynaecological surgery

Abstract: In this double-blind, randomized, parallel group study, we have investigated the antiemetic activity of the potent and selective NK1 receptor antagonist GR205171 25 mg i.v. compared with placebo in the treatment of established postoperative nausea and vomiting (PONV) in patients after major gynaecological surgery performed under general anaesthesia. The incidence of PONV in the study population was 65%. Thirty-six patients were treated with placebo or GR205171 (18 patients per group). GR205171 produced greater control of PONV than placebo over the 24-h assessment period. The stimuli for emesis after PONV are multifactorial and the efficacy of GR205171 in this study supports the broad spectrum potential for NK1 receptor antagonists in the management of postoperative emesis. GR205171 was well tolerated and no adverse events were reported that would preclude the further development of this agent.

Effect of omitting regular ACE inhibitor medication before cardiac surgery on haemodynamic variables and vasoactive drug requirements.

Abstract: Adverse events during coronary artery bypass graft (CABG) surgery have been described in patients receiving angiotensin converting enzyme (ACE) inhibitors, including hypotension on induction of anaesthesia and an increase in vasoconstrictor requirements after cardiopulmonary bypass (CPB). Omitting regular ACE inhibitor medication before surgery may improve cardiovascular stability during anaesthesia. We evaluated prospectively the effect of omitting regular ACE inhibitor medication before CABG surgery on haemodynamic variables and use of vasoactive drugs. We studied 40 patients with good left ventricular function, allocated randomly to omit or continue ACE inhibitor medication before surgery. Arterial pressure, cardiac output, systemic vascular resistance and use of vasoactive drugs were recorded during anaesthesia and in the early postoperative period. Patients who omitted their ACE inhibitors had greater mean arterial pressure during the study and required less vasopressors during CPB. However, these patients required more vasodilators to control hypertension after CPB and in the early postoperative period. There was no difference in hypotension on induction of anaesthesia or in the use of vasoconstrictors after CPB. We conclude that omitting ACE inhibitors before surgery did not have sufficient advantage to be recommended routinely.