Summary

Background and objective: Anaesthesia may affect the regulatory balance of postoperative immune response. The aim of this study was to investigate the effects of different volatile and non-volatile anaesthetic agents and particularly of clinically used agent combinations on the proliferation capacity and cytokine production of immune cells. Methods: Peripheral blood mononuclear cells from healthy donors were PHA-activated in the presence or absence of various concentrations of thiopental, propofol, fentanyl, sufentanil, sevoflurane, nitrous oxide and combinations of these anaesthetics. Cell proliferation was assessed by tritiated thymidine uptake. Interleukin-2 production and release of the soluble IL-2 receptor were determined by enzyme immunoassays and used as measures of lymphocyte activation. Results: Thiopental inhibited cell proliferation in a dose dependent manner (P < 0.001) and reduced sIL-2R release (2090–970 pg mL−1; P < 0.05). Propofol reduced sIL-2R release at the high concentration of 10 μg mL−1 (2220 pg mL−1–1780 μg mL−1; P < 0.05). Fentanyl and sufentanil did not compensate for or enhance the inhibitory effects of thiopental. Nitrous oxide, but not sevoflurane, reduced the proliferation of human peripheral blood mononuclear cells (P < 0.05). In combinations with thiopental or nitrous oxide, sevoflurane compensated the inhibitory effects of these two agents. Fentanyl, sufentanil, sevoflurane and nitrous oxide did not affect PHA-induced IL-2 and sIL-2 receptor release by human peripheral blood mononuclear cells. Conclusion: Thiopental and nitrous oxide have immunosuppressive activity. In contrast, sevoflurane may have a beneficial effect by alleviating the immunosuppressive effects of both substances.

Malignant hyperthermia is an autosomal-dominant inherited disorder of the skeletal muscle cell characterized by a hypermetabolic response to all commonly used inhalational anaesthetics and depolarizing muscle relaxants. The clinical syndrome includes muscle rigidity, hypercapnia, tachycardia and myoglobinuria as result of increased carbon dioxide production, oxygen consumption and muscle membrane breakdown. In human beings and animals susceptible to malignant hyperthermia, it is generally accepted that an increase in the level of myoplasmic free calcium is the cause of the syndrome. Various hypotheses have been proposed to account for the increase of intracellular calcium levels, e.g. a defect in the calcium release channel of the sarcoplasmic reticulum (ryanodine receptor), an abnormality of the excitation-contraction coupling mechanisms, or alterations in second messenger systems of skeletal muscles. This review gives an overview of the main features of this disease and recent advances in research including pathophysiology, treatment, diagnosis and genetics as well as association with other disorders.

Background and objective: Liver transplantation is characterized by several changes in intravascular blood volume due to vasodilatation based on neurohumoral mediators, intraoperative bleeding and anaesthesia technique effects. Today, with the transpulmonary indicator dilution technique, cardiac index (CIart) can be evaluated and preload assessed in terms of the intrathoracic blood volume index (ITBVI). The aim was to analyse in patients undergoing liver transplantation two preload variables, pulmonary artery occlusion pressure (PAOP) and ITBVI with respect to cardiac index (CIpa) and stroke volume index (SVIpa), the correlation between ITBVI and PAOP, and secondary the relationship between the changes (Δ) of ITBVI and PAOP and the changes of CIpa and SVIpa, and the relationships between ΔITBVI and ΔPAOP. The reproducibility and precision of all CIart and CIpa measurements were also evaluated.

Methods: A prospective study was performed in 60 patients monitored with a pulmonary artery catheter and with the PiCCO® system. The variables were evaluated with a linear regression model.

Results: Linear regression analysis between ITBVI-CIpa and ITBVI-SVIpa were r2 = 0.47 (P < 0.0001) and r2 = 0.55 (P < 0.0001) respectively, while PAOP poorly correlated to CIpa (r2 = 0.02), SVIpa (r2 = 0.015) and ITBVI (r2 = 0.002). Only changes in ITBVI were correlated with changes in CIpa (Δ1, r2 = 0.37; Δ2, r2 = 0.32), and SVIpa (Δ1, r2 = 0.60; Δ2, r2 = 0.47). The mean bias between CIart and CIpa was 0.13 L min−1 m−2 (2 SD = 1.04 L min−1m−2) (r2 = 0.86, P < 0.0001).

Conclusions: In comparison with PAOP, ITBVI seems a more reliable indicator of cardiac preload in patients undergoing liver transplantation.

Background and objective: Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Our hypothesis was that the renal vasodilating and natriuretic effects of fenoldopam mesylate, a selective dopamine (DA1) agonist, would preserve renal function in patients undergoing elective infrarenal aortic cross-clamping.

Methods: A prospective, randomized, double blind controlled clinical trial was performed. Twenty-eight ASA II-III patients undergoing elective aortic surgery requiring infrarenal aortic cross-clamping were studied. According to random allocation, patients received either fenoldopam (0.1 μg kg−1 min−1) or placebo intravenously prior to surgical skin incision until release of the aortic clamp. Plasma creatinine, creatinine clearance, urinary output, fractional excretion of sodium, and free water clearance were measured: (a) prior to admission to hospital; (b) during the period from insertion of the urinary catheter until application of the aortic cross-clamp; (c) during the period of aortic cross-clamping; (d) 0-4 h, and (e) 4-8 h after release of the clamp and on days 1, 2, 3, and 5 postoperatively.

Results: Fenoldopam (0.1 μg kg−1 min−1) administration was not associated with haemodynamic instability. On application of the aortic cross-clamp creatinine clearance decreased significantly in the placebo (83 ± 20 to 42 ± 29 mLmin−1 (mean ± SD)) (P < 0.01) but not in the fenoldopam group, and this decrease persisted for at least 8 h after release of the cross-clamp (83 ± 20 to 54 ± 33 mLmin−1 (mean ± SD)) (P < 0.05). Plasma creatinine concentration increased significantly from baseline on the first postoperative day in the placebo group (87 ± 12 to 103 ± 28 μmol L−1 (mean ± SD)) (P < 0.01) but not in the fenoldopam group.

Conclusions: These findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect during and after infrarenal aortic cross-clamping.

Summary

AstraZeneca (the manufacturer of Diprivan™) presents its review of the history of the so-called ‘propofol infusion syndrome’, highlighting the difficulties in analysing the incomplete information available. Theories as to its causality are presented and discussed; these include mitochondrial toxicity, mitochondrial defects, impaired tissue oxygenation and carbohydrate deficiency. A review of published and confidential safety data is presented and discussed; it concludes that the major risk factors for its development appear to be poor oxygen delivery, sepsis, serious cerebral injury and high propofol dosage. In some reports an increasing lipaemia was noted and was likely to be due to a failure of hepatic lipid regulation, possibly related to poor oxygenation and/or possibly a lack of glucose. In some cases an increasing lipaemia was the first indication of impending ‘propofol infusion syndrome’ onset and it should not be viewed as a benign sign. The lipaemia can lead to sequestration of propofol into the lipid phase, leading to lowered free propofol levels and apparent insensitivity to propofol. In conclusion AstraZeneca advocates good haemodynamic and oxygen delivery management, adequate glucose provision, adherence to recommended propofol dosing regimes together with active management of lipaemias to both prevent and treat ‘propofol infusion syndrome’.

Summary

Background and objective: This study clarifies the relationship between the neuromuscular blocking effects of rocuronium 0.6 mg kg−1 and its pharmacokinetics in patients with renal failure.

Methods: Seventeen healthy patients and 17 patients with renal failure were studied under propofol anaesthesia in this prospective open label study. Rocuronium 0.6 mg kg−1 was given after induction of anaesthesia. The train-of-four mechano-myographic response of the thumb to supramaximal stimulation of the ulnar nerve at 2 Hz every 12 s was measured. Venous blood samples (4 mL) were obtained at 0, 2, 4, 7, 10, 15, 20, 30, 60, 120, 180, 240 and 360 min after relaxant administration. Samples were centrifuged, separated and stored at −20°C until plasma levels of rocuronium and its metabolites were measured. Two- and three-exponential equations were used to describe the pharmacokinetic data in each group and these were compared to each other using the Wilcoxon signed rank sum test as was the pharmacodynamic data. P < 0.05 was significant.

Results: Onset of block was similar in both groups. Clinical duration and the time to recovery of the train-of-four to 70% were prolonged in the renal failure group compared to control; 49 vs. 32 min (P < 0.004, 95% confidential interval 17, difference 5–28) and 88 vs. 55 min (P < 0.001, 95% confidential interval 33, difference 17–50), respectively. Clearance of rocuronium was reduced by 39% in the renal failure patients compared to control, with an 84% increase in the mean residence time. The volume of distribution was unaffected by renal failure.

Conclusions: The duration of action of a bolus dose of 0.6 mg kg−1 rocuronium is increased significantly in patients with end-stage renal failure compared to healthy controls. This increase may be due to a decreased clearance of rocuronium, the disease process causing the renal failure and/or the medication which patients with renal failure need in their treatment.

Tramadol is a weak centrally acting analgesic and it might provide efficacious postoperative pain relief with minimal sedative effects in the use of intravenous patient-controlled analgesia (PCA). Sixty women scheduled to undergo microvascular breast reconstruction under standard general anaesthesia were enrolled in a study on the performance of patient-controlled analgesia with tramadol or morphine with special emphasis on drug- and technique-related side-effects. Seven patients were re-operated within the same day, leaving 25 patients in the tramadol group and 28 in the morphine group for comparison. When postoperative pain occurred, loading doses of either 10mg tramadol or 1mg morphine intravenous increments were administered in a double-blind fashion until the pain control was judged to be satisfactory by the patient. After that the patients received tramadol or morphine by a PCA apparatus (lockout 5 min, tramadol 450 μg kg−1, morphine 45 μg kg−1 bolus). In addition, all patients received 500mg paracetamol rectally, three times a day. The potency ratio of tramadol to morphine was found to be between 8.5 : 1 (loading) and 11 : 1 (PCA). There was neither a significant difference between the groups in the overall satisfaction of the analgesic medication nor in the visual analogue and verbal rate scales for pain. Women in the tramadol group had more nausea and vomiting during the administration of loading doses (P < 0.05) and more patients in the tramadol group (7) than in the morphine group (3)(NS) wanted to discontinue the PCA therapy before the end of the study due to nausea. Sedation or blurred vision prevented the performance of the psychomotor tests in 22 and 32% of the tramadol and morphine patients, respectively. The remaining patients performed similarly in the Digit Symbol Substitution Test. In women receiving intravenous PCA for analgesia after microvascular breast reconstruction tramadol and morphine provided comparable postoperative analgesia with similar sedative effects. However, tramadol was associated with a disturbingly high incidence of nausea and vomiting.

Summary

The centrally acting α2-adrenoceptor agonists clonidine and dexmedetomidine have been used with success to provide haemodynamic stability for patients undergoing surgery. Particularly in the case of patients with overt or underlying cardiac disease the actions of α2-adrenoceptor agonists, which include maintenance of stable systemic blood pressure and low heart rate and a reduction in overall oxygen consumption, can be expected to reduce the risk of procedure-related cardiac events. This expectation has been corroborated in clinical trials with clonidine, dexmedetomidine and mivazerol and meta-analyses; additional large controlled trials would be instructive in establishing a robust estimate of the scale of the benefit. In addition, α2-adrenoceptor agonists used as premedication have been shown to substantially reduce anaesthetic requirements among surgical patients, and the use of these agents has been associated with a reduced risk of postoperative delirium, which may be expected to improve considerably the postoperative course for at-risk patients. Dexmedetomidine is the only α2-adrenoceptor agonist currently approved for use in the intensive care unit. A distinctive feature of dexmedetomidine in that setting is that in addition to haemodynamic stability it confers a distinctive and advantageous quality of sedation: patients are tranquil but responsive to requests from attending staff. This review examines the pharmacological principles underlying the use of α2-adrenoceptor agonists as adjuncts to surgery and clinical experience in that indication.

Summary

Background and objective: This placebo-controlled study was performed to evaluate the efficacy of dexmedetomidine compared with meperidine and placebo in preventing postanaesthetic shivering. Methods: We studied 120 patients (ASA I–II) scheduled for elective abdominal or orthopaedic surgery of about 1–3 h duration. Forty patients in each group randomly received 1 μg kg−1 of dexmedetomidine, 0.5 mg kg−1 of meperidine or saline 0.9% as placebo, intravenously (i.v.). Mean arterial pressure, heart rate, oxygen saturation and central body temperature were measured. Extubation, awakening and orientation times, shivering, pain, recovery and sedation scores were recorded. Results: Postanaesthetic shivering was seen in 22 patients in the placebo group, four patients in the meperidine group and six patients in the dexmedetomidine group. Sedation scores were significantly higher in the dexmedetomidine group compared with meperidine and placebo groups. Both dexmedetomidine and meperidine caused a significantly prolonged extubation and awakening time compared with placebo. Also, dexmedetomidine caused a significantly prolonged orientation time compared with other two groups. Conclusion: Intraoperative intravenously administration of dexmedetomidine 1 μg kg−1 reduces postanaesthetic shivering as does meperidine 0.5 mg kg−1 in patients after major surgery.

The incidence of sore throat after the use of the laryngeal mask was assessed with a randomized trial in 839 patients. Sore throat occurred more often in women, older patients or after multiple insertion attempts. It was found that the frequency in women, but not in men, was lowered from 11.9% to 3.9% (P=0.012) by reducing intracuff pressure to the minimum required for an effective seal.

Summary

Background and objective: Anaesthesiology is considered a stressful occupation. Our purpose was to assess stress and burnout among Portuguese anaesthesiologists. Methods: A cross-sectional survey based on an anonymous questionnaire was sent to all Portuguese anaesthesiologists registered by the Portuguese Medical Association. Data on patient characteristics and professional variables, perceived stress (Perceived Stress Scale), the subscale of work satisfaction of the Pressure Management Indicator scale, burnout (Maslach Burnout Inventory) and main stress factors were collected. The proportion of participation was 31.8%. Results: The average value of perceived stress scale was 24.0 (range: 0–56). Among the 263 anaesthesiologists, 57.9% experienced emotional exhaustion, 44.8% lack of personal accomplishment and 90.9% depersonalisation. Lack of personal accomplishment increased with number of children among women but not among men; depersonalisation was more frequent among anaesthesiologists working in community hospitals and anaesthesiologists with leadership functions experienced less professional stress. Conclusion: There are stress conditions and burnout amongst Portuguese anaesthesiologists. The prevalence of depersonalisation was extremely high in the studied sample. Emotional exhaustion is partially explained by high perceived-stress and low satisfaction with organisation in the job according to Pressure Management Indicator scale.

Summary

Background and objective: Sedation is commonly used to facilitate diagnostic procedures in children. The aim of our study was to investigate sedation in children using propofol alone or combined with fentanyl or midazolam with regard to efficacy, adverse reactions or side-effects related to the drugs, ease of operation for the endoscopist, and time to discharge from the post-anaesthesia care unit. Methods: We prospectively studied 240 children, aged 1–12 yr of age, undergoing endoscopic procedures of the upper gastrointestinal tract. The patients were given an oral premedication with midazolam (0.5 mg kg−1) and were then randomly allocated to one of the three study groups: propofol alone (Group P), propofol with fentanyl 1 μg kg−1 (Group PF) or propofol with midazolam 0.1 mg kg−1 (Group PM). Additional doses of propofol given during the procedure were recorded. Adequacy of sedation and ease of procedure (easy, adequate, impossible) were evaluated by the endoscopist, who was blinded as to the drugs used. Results: The duration of the procedure and the recovery period were similar in the three groups. The number of patients requiring supplemental doses of propofol to permit safe completion of gastroscopy was 31 in Group P (=39%; eight of these required two additional doses), 14 in Group PM (=18%), and 11 in Group PF (=13%) (P < 0.05). There was a lower incidence of adverse events in Group PM and in Group PF than in Group P (P < 0.05). Conclusions: Propofol in combination with fentanyl or midazolam gives better sedation and ease of endoscopy than propofol alone.

Summary

Background and objective: Quality of acute pain management is far from being satisfactory. These deficits are not caused by the complexity of the medical problem but by difficulties in organization and hospital structures, sand procedures. Continuous quality improvement is a recommended tool to overcome such difficulties and to increase quality in the long run. This study reports the implementation of benchmarking-based continuous quality improvement to improve postoperative pain management at a university hospital. Methods: A specialised pain nurse interviewed patients of three surgical departments on the first day after surgery, and continuously assessed process and outcome quality parameters. A multidisciplinary team of anaesthetists, surgeons, nurses and pharmacists implemented a regular procedure of data analysing and internal benchmarking. Results and suggested improvements were fed back to the healthcare teams. Results: From 1998 to 2002, 6756 patients were assessed. Average pain on ambulation and maximal pain were 3.7 ± 2.4 and 5.0 ± 2.5 (mean ± SD) on a 11-point numeric rating scale. Pain intensity at rest was 1.9 ± 1.8. Over time, pain intensity on ambulation decreased (P = 0.022) whereas maximal pain and pain at rest remained unchanged. There was an increase in the number of patients who received non-opioid analgesia (P < 0.001). Conclusions: A continuous quality improvement process could be established and is now successfully used in clinical routine. Cornerstones of this project were frequent assessments of process and outcome parameters, regular benchmarking and implementation of feedback mechanisms. Changes in organization of medical management and multidisciplinary teamwork seem to be more important than medical or technical aspects.

We prospectively evaluated the effects of pneumoperitoneum and reverse Trendelenburg position on cardiopulmonary function in 20 ASA physical status II–III morbidly obese patients (body mass index > 35 kg m−2) undergoing laparoscopic gastric banding. After general anaesthesia was induced, patients' lungs were ventilated using intermittent positive pressure ventilation (at measurement times, the following parameters were used: tidal volume 12 mL kg−1 ideal body weight, respiratory rate of 12 bpm, an inspiratory to expiratory time ratio of 1 : 2). Haemodynamic variables, blood gas parameters, and lung/chest compliance were recorded: in the supine position, after induction of general anaesthesia (T0, baseline) and induction of pneumoperitoneum (T1); after placing the patient in a 25° reverse Trendelenburg position (T2); during the surgical time (T3); before deflating the abdomen (T4); after pneumoperitoneum resolution (T5), and before the end of anaesthesia, with the patient supine (T6). The PaO2, PaO2/FiO2 ratio, and lung/chest compliance decreased during the study. After the pneumoperitoneum had been resolved, lung/chest compliance but not oxygenation parameters returned to baseline values. The arterial to end-tidal CO2 tension difference progressively increased from 0.38 ± 0.3 kPa (2.85 ± 2.25 mmHg) (T0) to 0.63 ± 0.3 kPa (4.73 ± 2.25 mmHg) (T6). In morbidly obese patients, undergoing laparoscopic gastric banding, a CO2 pneumoperitoneum markedly affected gas exchange and lung/chest compliance, while positioning the patient in a 25° reverse Trendelenburg position had no beneficial effects.

Sepsis, a systemic inflammatory response to infection, is a leading cause of death in intensive care units. Recent investigations into the pathogenesis of sepsis reveal a biphasic inflammatory process. An early phase is characterized by pro-inflammatory cytokines (e.g. tumour necrosis factor-α), whereas a late phase is mediated by an inflammatory high-mobility group box 1 and an anti-inflammatory interleukin-10. Inflammation aberrantly activates coagulation cascades as sepsis progresses. This dual inflammatory response concomitant with dysregulated coagulation partially accounts for unsuccessful anti-cytokine therapies that have solely targeted early pro-inflammatory mediators (e.g. tumour necrosis factor-α). In contrast, activated protein C, which modifies both inflammatory and coagulatory pathways, has improved survival in patients in severe sepsis. Inhibition of the late mediator high-mobility group box 1 improves survival in established sepsis in pre-clinical studies. In addition, recent advances in molecular medicine have shed light on two novel experimental interventions against sepsis. Accelerated apoptosis of lymphocytes has been shown to play an important role in organ dysfunction in sepsis and techniques to suppress apoptosis have improved survival rate in sepsis models. The vagus nerve system has also been shown to suppress innate immune response through endogenous release and exogenous administration of cholinergic agonists, ameliorating inflammation and lethality in sepsis models.

Summary

Background and objective: An evaluation of post-craniotomy analgesia within the University Hospital of Wales Neurosurgical Unit, Cardiff, found that many patients were experiencing moderate to severe pain post-craniotomy. It was therefore decided to undertake a nationwide survey of analgesic practices in order to establish best practice guidelines and benchmark with other units.

Method: A postal questionnaire was sent to the senior nurse of every Neurosurgical Directorate within the UK inquiring about the current, standard analgesic practices for post-craniotomy patients in their unit.

Results: Completed replies were received from 23 of the 33 centres (70%). Intramuscular (i.m.) codeine phosphate was found to be the principal first-line analgesic used post-craniotomy. Only three centres used morphine as the first-line analgesic and only one centre used patient controlled analgesia routinely. The majority of centres (82%) used balanced analgesia. Pain assessments were only carried out in 57% of centres and no centre used a validated pain assessment tool specifically for dysphasic patients.

Conclusions: Codeine phosphate continues to be the mainstay of post-craniotomy analgesia, however, it is proposed that patient controlled analgesia with morphine is an efficacious and safe alternative.