The effect of metrics-based feedback on acquisition of sonographic skills relevant to performance of ultrasound-guided axillary brachial plexus block.

The objective of this study was to examine the effect of metrics-based vs. non-metrics-based feedback on novices learning predefined competencies for acquisition and interpretation of sonographic images relevant to performance of ultrasound-guided axillary brachial plexus block. Twelve anaesthetic trainees were randomly assigned to either metrics-based-feedback or non-metrics-based feedback groups. After a common learning phase, all participants attempted to perform a predefined task that involved scanning the left axilla of a single volunteer. Following completion of the task, all participants in each group received feedback from a different expert in regional blocks (consultant anaesthetist) and were allowed to practise the predefined task for up to 1 h. Those in the metrics-based feedback group received feedback based on previously validated metrics, and they practised each metric item until it was performed satisfactorily, as assessed by the supervising consultant. Subsequently, each participant attempted to perform ultrasonography of the left axilla on the same volunteer. Two trained consultant anaesthetists independently scored the video recording pre- and post-feedback scans using the validated metrics list. Both groups showed improvement from pre-feedback to post-feedback scores. Compared with participants in the non-metrics-based feedback group, those in the metrics-based feedback group completed more steps: median (IQR [range]) 18.8 (1.5 [17-20]) vs. 14.3 (4.5 [11-18.5]), p = 0.009, and made fewer errors 0.5 (1 [0-1.5]) vs. 1.5 (2 [1-6]), p = 0.041 postfeedback. In this study, novices' sonographic skills showed greater improvement when feedback was combined with validated metrics.

Construct validity of a novel assessment tool for ultrasound-guided axillary brachial plexus block.

The purpose of this study was to examine the construct validity and reliability of a novel metrics-based assessment tool, previously developed for ultrasound-guided axillary brachial plexus block. Five expert and eight novice anaesthetists performed a total of 18 ultrasound-guided axillary brachial plexus blocks on the same number of patients. A trained investigator video-taped procedures according to a pre-defined protocol. Two trained consultant anaesthetists independently scored the videos using the assessment tool. Compared with novices, experts completed more steps (mean 41.0 vs. 33.1, p = 0.001), had fewer procedural errors (2.8 vs. 7.9, p < 0.0001), had fewer critical errors (0.8 vs. 1.3, p = 0.030), and fewer total errors (3.5 vs. 9.1, p < 0.0001). The mean inter-rater reliability for scoring of experts' performance was 0.91, for novices' performance was 0.84, and for all performance combined (n = 18) was 0.88. This assessment tool is valid, and discriminates reliably between expert and novice performance for placement of ultrasound-guided axillary brachial plexus blocks.

Effect of epidural analgesia on change in Mallampati class during labour.

Mallampati class has been shown to increase during labour. Epidural analgesia might influence this change. The aim of our study was to compare the change in Mallampati class during labour in parturients who did and did not receive epidural analgesia and study the association of these changes with pre-defined clinical characteristics. We performed a prospective observational study of 190 parturients. Using standard methodology, photographs of the upper airway were taken with a digital camera during early labour and within 90 min of delivery. Two to three consultant anaesthetists, blinded to the origin of the photographs, evaluated the images obtained and assigned a Mallampati class to each. Overall, Mallampati class increased in 61 (32.1%), decreased in 18 (9.5%) and did not change in 111 (58.4%) parturients (p<0.001). The proportions of parturients in the epidural and non-epidural groups who demonstrated an increase, decrease and no change in Mallampati class were similar. Of the relationships between change in Mallampati class and the other factors studied, only the total dose of epidural levobupivacaine during labour demonstrated a weak positive correlation 0.17 (p=0.039) with Mallampati class. This study confirms that labour is associated with an increase in the Mallampati class in approximately one third of parturients. Our findings indicate that having an epidural does not influence the likelihood of a change in Mallampati class during labour.

Validation of a clinical assessment tool for spinal anaesthesia.

BACKGROUND: There is a need for a procedure-specific means of assessment of clinical performance in anaesthesia. The aim of this study was to devise a tool for assessing the performance of spinal anaesthesia, which has both content and construct validity. METHODS: The clinical assessment tool was generated using a focus group discussion of practicing anaesthetists. The tool comprised three components: a checklist of 11 pre-defined errors, two time intervals and a six-item global rating scale (GRS). Thirty-one anaesthetists at three different levels of experience underwent testing using the clinical assessment tool: novice (n=10), intermediate (n=10) and expert (n=11). RESULTS: The error checklist and GRS scores but not the time intervals were significantly different between the three groups (P<0.005). CONCLUSION: The error checklist and GRS form the basis for a procedure-specific assessment tool for spinal anaesthesia.

Can state or response entropy be used as a measure of sleep depth?

SUMMARY: In this prospective observational study we examined the potential of the spectral entropy measures 'state' and 'response' entropy (Entropy monitor), as measures of sleep depth in 12 healthy adult subjects. Both median state and response entropy values varied significantly with sleep stage (p = 0.017 and p = 0.014 respectively; ANOVA). Median state or response entropy did not decrease significantly during the transition from awake to stage I sleep (p > 0.017). State entropy values decreased significantly between sleep stages I and II (p < 0.001). Both state and response entropy values were significantly less (40 and 45 arbitrary units respectively) in stage III (slow wave sleep) vs stage II sleep (p = 0.008). We conclude that state and response entropy values, when expressed as a function of time, may be a useful means of quantifying aspects of sleep.

Behaviour of spectral entropy, spectral edge frequency 90%, and alpha and beta power parameters during low-dose propofol infusion.

BACKGROUND: In this study we analyse the behaviour, potential clinical application and optimal cortical sampling location of the spectral parameters: (i) relative alpha and beta power; (ii) spectral edge frequency 90%; and (iii) spectral entropy as monitors of moderate propofol-induced sedation. METHODS: Multi-channel EEG recorded from 12 ASA 1 (American Society of Anesthesiologists physical status 1) patients during low-dose, target effect-site controlled propofol infusion was used for this analysis. The initial target effect-site concentration was 0.5 microg ml(-1) and increased at 4 min intervals in increments of 0.5 to 2 microg ml(-1). EEG parameters were calculated for 2 s epochs in the frequency ranges 0.5-32 and 0.5-47 Hz. All parameters were calculated in the channels: P4-O2, P3-O1, F4-C4, F3-C3, F3-F4, and Fp1-Fp2. Sedation was assessed clinically using the OAA/S (observer's assessment of alertness/sedation) scale. RESULTS: Relative beta power and spectral entropy increased with increasing propofol effect-site concentration in both the 0.5-47 Hz [F(18, 90) = 3.455, P<0.05 and F(18, 90) = 3.33, P<0.05, respectively] and 0.5-32 Hz frequency range. This effect was significant in each individual channel (P<0.05). No effect was seen of increasing effect-site concentration on relative power in the alpha band. Averaged across all channels, spectral entropy did not outperform relative beta power in either the 0.5-32 Hz [Pk=0.79 vs 0.814 (P>0.05)] or 0.5-47 Hz range [Pk=0.81 vs 0.82 (P>0.05)]. The best performing indicator in any single channel was spectral entropy in the frequency range 0.5-47 Hz in the frontal channel F3-F4 (Pk=0.85). CONCLUSIONS: Relative beta power and spectral entropy when considered over the propofol effect-site range studied here increase in value, and correlate well with clinical assessment of sedation.

Determinants of learning to perform spinal anaesthesia: a pilot study.

BACKGROUND AND OBJECTIVE: This study examined attitudes and views held by stakeholders regarding their experience of training in spinal anaesthesia. The aim was to identify key factors related to learning and teaching processes which were perceived to influence the acquisition of competence in spinal anaesthesia. METHODS: The study was carried out at a busy acute tertiary referral teaching hospital over a period of 1 yr. It applied a qualitative research approach in three phases, namely (i) completion of preliminary questionnaires, (ii) completion of focused questionnaires and (iii) focus group discussions. RESULTS: Five factors were perceived to be critical 'determinants of learning': (i) the existence of a formal, structured training programme; (ii) time constraints/theatre efficiency; (iii) trainer-trainee interaction; (iv) patient safety/trainee/trainer stressors; and (v) visualization of the anatomy and procedure. CONCLUSION: The study highlighted the need for a formal and structured training programme in spinal anaesthesia, through which many of the undesirable and discouraging factors (such as stress, adverse trainer-trainee interaction and time constraints) identified in the study could be minimized. Further studies are needed to validate the results in other hospital settings, as well as to define the relative importance of each of the proposed determinants and their interrelationships.

The effect of midazolam on cerebral endothelial (P-selectin and ICAM-1) adhesion molecule expression during hypoxia-reperfusion injury in vitro.

BACKGROUND AND OBJECTIVE: Hypoxia-reperfusion injury is an important determinant of secondary brain injury. In the acute phase of cerebral reperfusion, pro-inflammatory events enhance expression of cerebral endothelial (intercellular adhesion molecule-1 and P-selectin) adhesion molecules, which play an important role in brain hypoxia-reperfusion injury. Midazolam is the most commonly used sedative in patients with brain injury. The objective of this investigation was to examine the effect of midazolam on the expression of cerebral endothelial intercellular adhesion molecule-1 and P-selectin during hypoxia-reperfusion injury in vitro. METHODS: The up-regulation of mouse cerebral endothelial cells intercellular adhesion molecule-1 and P-selectin was assessed following hypoxia-reoxygenation (hypoxia-reperfusion). Cells were pre-treated with three different concentrations of midazolam (0, 5 and 50 microg mL(-1)) prior to hypoxia. Flow cytometry was used to estimate adhesion molecule expression mean channel fluorescence. Data are presented as mean +/- SD. RESULTS: Mouse cerebral endothelial cell intercellular adhesion molecule-1 and P-selectin expression was greater after exposure to hypoxia-reoxygenation compared to normoxia (mean channel fluorescence) 241 +/- 12 vs. 140 +/- 7 and 120 +/- 14 vs. 46 +/- 7, respectively, P < 0.05. Intercellular adhesion molecule-1 and P-selectin expression was decreased by midazolam (5 microg mL(-1)) pre-incubation compared to control, mean channel fluorescence 184 +/- 10 vs. 241 +/- 12 and 51 +/- 7 vs. 120 +/- 14, respectively, P < 0.05. Midazolam at 50 microg mL(-1) had the same effect as 5 microg mL(-1). CONCLUSION: Pre-treatment with midazolam diminishes increased expression of cerebral endothelial intercellular adhesion molecule-1 and P-selectin expression following hypoxia-reoxygenation.

The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function.

BACKGROUND: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass elicits a potent reperfusion injury and inflammatory response, more intense in patients with impaired myocardial function. Propofol has antioxidant properties which may attenuate such a response. METHODS: In total, 27 patients with impaired left ventricular function undergoing CABG were randomly allocated to receive either target-controlled infusion propofol (P) or saline (S) immediately before aortic cross-clamp release until 4 h after reperfusion. Troponin-I, Urinary 8-epi PGF-2alpha isoprostane, coronary sinus and systemic malondialdehyde concentrations, Interleukin-6 (IL-6), -8 and -10 concentrations and leucocytes function studies (neutrophil respiratory burst, phagocytosis, CD-11b and CD-18 expression) were measured. RESULTS: Propofol decreased MDA coronary sinus concentration at 1, 3 and 5 min after reperfusion (P<0.01); 60 min after reperfusion a significant difference between the two groups in systemic MDA concentrations was also seen. IL-6 concentration increases were significantly greater in Group S than Group P, 4 h after reperfusion [1118 (1333) pg ml(-1) vs 228 (105) pg ml(-1), P<0.01]. Serum IL-8 concentrations did not increase significantly in either group. Compared with baseline values IL-10 concentrations decreased after reperfusion but the values were higher in the propofol group than in the control group [22 (16) vs 11 (4) pg ml(-1), P<0.05]. No difference in leucocyte function or urinary isoprostane concentrations was demonstrated. CONCLUSION: Propofol attenuates free-radical-mediated lipid peroxidation and systemic inflammation in patients with impaired myocardial function undergoing CABG.

The influence of propofol on the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in reoxygenated human umbilical vein endothelial cells.

BACKGROUND: Leucocytes are a pivotal component of the inflammatory cascade that results in tissue injury in a large group of disorders. Free radical production and endothelial activation promote leucocyte-endothelium interactions via endothelial expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) which augment these processes, particularly in the setting of reperfusion injury. Propofol has antioxidant properties which may attenuate the increased expression of these molecules that is observed. METHODS: Cultured human umbilical vein endothelial cells were exposed to 20 h of hypoxia, then returned to normoxic conditions. Cells were treated with saline, Diprivan 5 microg mL(-1) or propofol 5 microg mL(-1), for 4 h after reoxygenation and were examined for ICAM-1 and VCAM-1 expression. RESULTS: Hypoxia did not increase the expression of ICAM-1/VCAM-1. ICAM-1 expression peaked 12 h after reoxygenation (21.75(0.6) vs. 9.6(1.3), P = 0.02). Propofol, but not Diprivan, prevented this increase (8.2(2.9) vs. 21.75(0.6), P = 0.009). VCAM-1 expression peaked 24 h after reoxygenation (9.8(0.9) vs. 6.6(0.6), P = 0.03). Propofol and Diprivan prevented this increase, with no difference between the two treatments observed (4.3(0.3) and 6.4(0.5) vs. 9.8(0.9), P = 0.001, 0.02, respectively). CONCLUSION: These effects are likely to be attributable to the antioxidant properties of propofol, and suggest that propofol may have a protective role in disorders where free radical mediated injury promotes leucocyte-endothelium adhesive interactions.

The influence of propofol on P-selectin expression and nitric oxide production in re-oxygenated human umbilical vein endothelial cells.

BACKGROUND: Reperfusion injury is characterized by free radical production and endothelial inflammation. Neutrophils mediate much of the end-organ injury that occurs, requiring P-selectin-mediated neutrophil-endothelial adhesion, and this is associated with decreased endothelial nitric oxide production. Propofol has antioxidant properties in vitro which might abrogate this inflammation. METHODS: Cultured human umbilical vein endothelial cells were exposed to 20 h of hypoxia and then returned to normoxic conditions. Cells were treated with saline, Diprivan 5 microg/l or propofol 5 microg/l for 4 h after re-oxygenation and were then examined for P-selectin expression and supernatant nitric oxide concentrations for 24 h. P-selectin was determined by flow cytometry, and culture supernatant nitric oxide was measured as nitrite. RESULTS: In saline-treated cells, a biphasic increase in P-selectin expression was demonstrated at 30 min (P = 0.01) and 4 h (P = 0.023) after re-oxygenation. Propofol and Diprivan prevented these increases in P-selectin expression (P < 0.05). Four hours after re-oxygenation, propofol decreased endothelial nitric oxide production (P = 0.035). CONCLUSION: This is the first study to demonstrate an effect of propofol upon endothelial P-selectin expression. Such an effect may be important in situations of reperfusion injury such as cardiac transplantation and coronary artery bypass surgery. We conclude that propofol attenuates re-oxygenation-induced endothelial inflammation in vitro.

S100beta and nitric oxide product concentrations following cerebral aneurysm clipping in patients with subarachnoid haemorrhage: a pilot study.

OBJECTIVE: The objective of this investigation was to determine the efficacy of S100beta and nitric oxide product (nitrate and nitrite [NOx]) concentrations as markers of brain injury following cerebral aneurysm clipping in patients with spontaneous subarachnoid haemorrhage. METHODS: Fifteen patients with spontaneous subarachnoid haemorrhage were studied. Blood samples were obtained for estimation of serum S100beta (microg/L) and nitric oxide product (nitrate and nitrite [NOx]) (microM) concentrations immediately preoperatively (baseline) and then 10 minutes, 2, 6 and 12 hr postoperatively and daily thereafter for five days. Neurological outcome was assessed three months after surgery by the Glasgow Outcome Scale (GOS) (poor outcome, grade 1 - 3 and good outcome as grade 4 - 5). Data were analysed using the Mann-Whitney-U-test. RESULTS: S100beta concentrations were greater at two hours postoperatively compared to baseline (0.33 +/- 0.16 vs 0.25 +/- 0.04)(P = 0.02). S100beta concentrations were similar in good and poor neurological outcome groups as defined by GOS at three months. NOx concentrations were less at 12 hours postoperatively compared to baseline (9.81 +/- 3.25 vs 12.74 +/- 2.9)(P = 0.03). NOx concentrations were greater on the fourth and fifth postoperative days compared to baseline (t0) (17.22 +/- 7.9, 12.74 +/- 2.9 vs 9.81 +/- 3.25) (P < 0.05). NOx concentrations were greater in patients with a poor neurological outcome (n = 4) compared to the good outcome group (n = 11) (24.7 +/- 4.9 vs. 11.3 +/- 3.3)(P = 0.04). CONCLUSIONS: S100beta and NOx concentrations increase after cerebral aneurysm clipping in patients with spontaneous SAH. Increased nitric oxide product concentrations were associated with subsequent poor neurological outcome.

Tramadol as adjunct to psoas compartment block with levobupivacaine 0.5%: a randomized double-blinded study.

BACKGROUND: Tramadol has been administered peripherally to prolong analgesia after brachial plexus and neuraxial blocks. Our aim was to evaluate the systemic and perineural effects of tramadol as an analgesic adjunct to psoas compartment block (PCB) with levobupivacaine. METHODS: In a randomized, prospective, double-blinded trial, 60 patients (ASA I-III), aged 49-88 yr, undergoing primary total hip or knee arthroplasty underwent PCB and subsequent bupivacaine spinal anaesthesia. Patients were randomized into three groups. Each patient received PCB with levobupivacaine 0.5%, 0.4 ml kg(-1). The control group (group L, n=21) received i.v. saline, the systemic tramadol group (group IT, n=19) received i.v. tramadol 1.5 mg kg(-1) and the perineural tramadol group (group T, n=20) received i.v. saline and PCB with tramadol 1.5 mg kg(-1). Postoperatively patients received regular paracetamol 6-hourly and diclofenac sodium 12-hourly. Time to first morphine analgesia, 24-hour morphine consumption, sensory block, pain and sedation scores and haemodynamic parameters were recorded. RESULTS: Time (h) to first morphine analgesia was similar in the three groups [mean (SD)]: group L, 11.2 (6.6); group T, 14.5 (8.0); group IT, 14.6 (6.8); P=0.35. Twenty-four-hour cumulative morphine (mg) consumption was also similar in the three groups [group L, 21.9 (10.1); group T, 19.8 (6.7), group IT, 16.5 (9.5)], as were durations of sensory and motor block. There were no differences in the incidence of adverse effects except that patients in group IT were more sedated at 14 h than group L (P=0.02). CONCLUSION: We conclude that our data do not support a clinically important local anaesthetic or peripheral analgesic effect of tramadol as adjunct to PCB with levobupivacaine 0.5%.

A comparison of the effects of ranitidine and omeprazole on volume and pH of gastric contents in elective surgical patients.

BACKGROUND AND OBJECTIVE: In cases of aspiration of gastric contents the risk of pneumonitis is dependent on the pH and volume of the gastric contents. Omeprazole and rantidine each decrease gastric volume and increase gastric pH. We evaluated the efficacy of preoperative administration of omeprazole (60 mg) or ranitidine (150 mg) in the prophylaxis of aspiration pneumonitis. METHODS: Data were obtained from 75 elective female surgical patients randomly allocated to one of three groups, who received either omeprazole 60 mg orally, or ranitidine 150 mg orally, or neither, on the evening prior to, and on the morning of, surgery. Gastric volume and pH was measured using blind aspiration. RESULTS: Both pH < 2.5 and volume > 25 mL were present in none of the patients in either the ranitidine or omeprazole groups, compared to 15 of 25 control patients (P < 0.0001). CONCLUSIONS: Preoperative oral administration of omeprazole (60 mg) or ranitidine (150 mg) reduced residual gastric content volume and increased pH > 2.5, possibly reducing the effects of pulmonary aspiration of gastric contents.

The efficacy of nicorandil, calcium chloride and nitroglycerin in treatment of ropivacaine-induced cardiotoxicity.

BACKGROUND AND OBJECTIVE: The amide-linked local anaesthetics, bupivacaine and ropivacaine, can cause depression of cardiac contractility and dysrhythmias. In a previous study, we observed decreased contractility and ST segment depression following ropivacaine administration in anaesthetized dogs. The efficacy of intravenous (i.v.) and intracoronary nicorandil (30 and 100 microg kg(-1)), i.v. nitroglycerin (glyceryl trinitrate) (5 microg kg(-1)) and calcium chloride (1, 2 and 4 mmol) in reversing the cardiotoxic effects of intracoronary ropivacaine were studied following the administration of intracoronary ropivacaine. METHODS: Six dogs were studied. The dogs were anaesthetized with i.v. pentobarbital (30 mg kg(-1)). A left-sided thoracotomy was performed and the left circumflex coronary was cannulated. For each dog, the dose of ropivacaine was identified, which produced measurable cardiotoxicity. In each case, ropivacaine was followed by one of the three resuscitation drugs. The effects of each resuscitation drug on ST segments and left ventricular contractility (dP/dt) produced by ropivacaine alone were compared with those produced by ropivacaine followed by each of the three resuscitation drugs using Fisher's exact test. RESULTS: The doses of ropivacaine required to produce depression of left ventricular dP/dt and ST segments ranged from 1 to 8 mg. Ropivacaine-induced depression of left ventricular contractility (dP/dt) was more rapidly and completely reversed by calcium chloride than by either nitroglycerin or nicorandil (P = 0.008). CONCLUSIONS: Calcium chloride may be effective in the treatment of inadvertent intravascular administration of amide local anaesthetic agents.

Effects of fenoldopam on renal blood flow and its function in a canine model of rhabdomyolysis.

BACKGROUND AND OBJECTIVE: Our hypothesis was that fenoldopam, a selective DA1 agonist, would protect against rhabdomyolysis-induced renal injury. METHODS: We studied the effects of intravenous fenoldopam (0.1-1.0 microg kg(-1) min(-1)) or saline on renal blood flow and function in 10 anaesthetized Labrador dogs in whom rhabdomyolysis and myoglobinuric acute renal failure had been induced by administration of glycerol 50% (10mL kg(-1)) intramuscularly. Haemodynamic measurements including renal blood flow and derived parameters of renal function including creatinine clearance were recorded before and for the 30 min following glycerol injection, and during the 3 h following commencement of each infusion. Serum malondialdehyde concentrations were measured before and 15 min after glycerol intramuscularly, and 30 and 150 min after commencement of the infusion. RESULTS: In the fenoldopam group, creatinine clearance was less than placebo at 1 and 2 h after commencing the infusion (12.7 +/- 11.5 versus 31.3 +/- 9.9 mL min(-1), P = 0.04; 8.5 +/- 5.3 versus 20.1 +/- 7.4 mL min(-1), P = 0.03). A 140-fold increase in serum malondialdehyde concentration occurred in one dog (fenoldopam group). CONCLUSION: Fenoldopam increased the severity of the renal injury in this canine model of myoglobinuric acute renal failure.

Elimination of alfentanil delivered by infusion is not altered by the chronic administration of atorvastatin.

BACKGROUND AND OBJECTIVE: Statins are prescribed for patients with hypercholesterolemia. Atorvastatin is metabolized by cytochrome P4503A4 and inhibits P4503A4 activity in vitro. Alfentanil is a potent opioid used in clinical anaesthetic practice and is also metabolized by P4503A4. This study tested the hypothesis that chronic atorvastatin administration inhibits the metabolism of alfentanil. METHODS: Sixteen patients undergoing elective surgery were studied as matched pairs. One member of each pair was maintained on standard doses of atorvastatin for at least 4 months. Each patient received an alfentanil bolus (80 microg kg(-1)) intravenously (i.v.), followed by an alfentanil infusion (0.67 microg kg(-1) min(-1)) for 90 min. Serial plasma alfentanil concentrations were measured using gas chromatography-nitrogen phosphorous detection. Pharmacokinetic parameters were calculated using two-compartment linear modelling. RESULTS: One patient and the corresponding match were excluded from the analysis. The elimination half-life of alfentanil was similar in the control and atorvastatin groups (98.8 +/- 12.4 versus 98.3 +/- 11.3 min, respectively). The clearance (Cl), volume of distribution at steady-state (Vdss) and area under the curve (AUC) were similar in the two groups (Cl = 0.20 (+/- 0.06) and 0.22 (+/- 0.04) L min(-1), Vdss = 0.38 (+/- 0.07) and 0.39 (+/- 0.07) L kg(-1), AUC = 0.05 (+/- 0.02) and 0.04 (+/- 0.01) mg min mL(-1)). CONCLUSIONS: Concurrent atorvastatin administration does not alter the pharmacokinetics of alfentanil in patients undergoing elective surgery.

The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam.

Midazolam is a commonly used anaesthetic agent and is metabolised by the 3A4 isoform of the cytochrome P450 enzyme system. Atorvastatin is also metabolised by cytochrome P450 3A4 and, in vitro, atorvastatin inhibits the cytochrome P450 3A4-mediated metabolism of mexazolam. We hypothesised that concurrent administration of atorvastatin and midazolam would result in altered midazolam pharmacokinetics. Fourteen patients scheduled to undergo general anaesthesia for elective surgery were recruited in a matched pair design to receive intravenous midazolam (0.15 mg.kg-1). Of these patients, seven were taking long-term atorvastatin. Atorvastatin patients demonstrated a greater area under the curve (889.4 (standard deviation 388.6) ng-h.ml-1) vs. control patients (629.1 (standard deviation 197.2) ng-h.ml-1) (p < 0.05). Patients taking atorvastatin also demonstrated a decreased clearance (0.18 (standard deviation 0.08) l-kg. h-1) vs. control patients (0.27 (standard deviation 0.08) l-kg.h-1) (p < 0.05). This study suggests that chronically administered atorvastatin decreases the clearance of intravenously administered midazolam.

Benzodiazepines inhibit the rate of neutrophil apoptosis.

BACKGROUND: Benzodiazepines, which are commonly administered perioperatively, can depress immune function. Neutrophil apoptosis plays a central role in the regulation of inflammation. This is particularly important during and after surgery. AIM: To examine the effects of benzodiazepines (midazolam and diazepam) on neutrophil apoptosis. METHODS: Venous blood samples were withdrawn from patients scheduled to undergo elective surgery, (a) immediately prior to, and 10 minutes after administration of midazolam 0.2 mg/kg intravenously (n=11) and (b) immediately prior to, and 60 minutes after administration of diazepam 10 mg p.o. (n=10). Neutrophil apoptosis was measured by Annexin V-FITC after 1 and 12 hours in culture. RESULTS: The percentage of apoptotic cells was significantly less after midazolam at 12% (11.9) hours in culture compared to pre-midazolam 29.7% (13.3) (p<0.05). After diazepam, the rates of neutrophil apoptosis were also significantly less after 12 hours in culture (p<0.05). CONCLUSION: Administration of benzodiazepines in clinically relevant doses inhibits neutrophil apoptosis. In the perioperative period, this may influence the inflammatory response to surgery.