Summary

Background and objective: The purpose of the present study was to determine the pharmacokinetics of the μ-agonist opioid pirinitramide (piritramide) after prolonged administration.

Methods: Nine patients requiring intensive care therapy and artificial ventilation for several days received piritramide with a median infusion rate of 5 mg h−1 (range 4.8–10 mg h−1) for a median period of 69.9 h (range 49–89 h) for analgesia and sedation. After the end of the infusion, frequent arterial blood samples were withdrawn for 96 h and assayed for piritramide using a gas chromatographic method. Standard compartmental models were fitted to the individual concentration–time courses to characterize the elimination of piritramide after prolonged administration.

Results: The concentration–time course after the end of the infusion was adequately described with a three-compartment model in eight patients and a two-compartment model in one patient (standard two-stage geometric mean and 16–84% quantile: volumes of distribution V1 = 47.9 (26.8–85.8) L, V2 = 402 (241–672) L, V3 = 332 (124–885) L; clearances Cl1 = 66.5 (53.2–83.0)L h−1, Cl2 = 215 (125–369)L h−1, Cl3 = 18.4 (9.2–36.8) L h−1). Both the steady-state volume of distribution (782 L) and the terminal elimination half-life (17.4 h) were larger than predicted from single bolus pharmacokinetic studies (412.5 L and 10.4 h, respectively), the context-sensitive half-time after more than 72 h of administration was 32% shorter than predicted (285 vs. 420 min).

Conclusions: Despite increasing terminal elimination half-life and volume of distribution at steady state (increasing drug load for a given plasma concentration), the context-sensitive half-time of piritramide after3 days of administration is lower than predicted from bolus kinetics, making the drug a suitable candidate for intensive care unit analgesia.

Summary

Although local anaesthesia is mentioned in historical manuscripts, it is only a hundred years since Bier first reported the intrathecal use of local anaesthetic agents. This has been followed by a rapid progression in the art and science of spinal anaesthesia. Isomerically pure agents with favorable clinical profiles, such as ropivacaine and levobupivacaine are now available. Spinal anaesthesia is commonly used in a variety of situations, including orthopaedic, abdominal, gynaecological surgery, Caesarean section and the relief of pain in childbirth. Hyperbaric solutions of local anaesthetics appear to produce more consistent results than plain solutions and the addition of other drugs, such as opioids and clonidine may improve analgesia. In addition to traditional spinal anaesthesia, local anaesthetics are now being evaluated in continuous spinal anaesthesia and combined epidural–spinal anaesthesia. This article reviews clinical experience with levobupivacaine and ropivacaine. Compared with levobupivacaine, ropivacaine generally produces a less intense motor block of shorter duration, which has advantages for earlier mobilization and discharge from hospital and may be particularly useful in obstetrics and ambulatory surgery.

Summary

Sepsis is an infection-induced syndrome characterized by a generalized inflammatory state. The normal reaction to infection involves a series of complex immunological processes. A potent, complex immunological cascade ensures a prompt protective response to microbial invasion in human beings. Although activation of the immune system during microbial invasion is generally protective, septic shock develops in a number of patients as a consequence of excessive or poorly regulated immune response to the offending organism. This unbalanced reaction may harm the host through a maladaptive release of endogenously generated inflammatory compounds. Early recognition of the syndrome is of key importance to promptly start appropriate management. Timely, aggressive resuscitation to preserve organ function remains a fundamental principle in the care of septic patients. The specific treatment is directed at identifying and treating the underlying disorder. The physician should investigate diligently for the presence of active infection using modern imaging methods and other diagnostic studies to localize the site of infection and to obtain adequate culture specimens from potential infective sources. Early administration of appropriate, effective antibiotic therapy is important in the management of septic patients. Infected fluid collections and/or infected necrotic tissues should be drained or debrided without delay. Adequate nutritional support is indicated in the management of the septic patient. A number of adjuvant therapies, aimed at blunting/downregulating the host immune response to bacterial infection are currently under intensive investigation; however, the complexity of immunological defences and the potential for complementary interaction of the different components of the inflammatory cascade make the development of these pharmacological interventions difficult.

Summary

Perioperative brain protection refers to prophylactic measures instituted during the perioperative period to prevent or reduce ischaemic damage and to improve neurological outcome. In that context, strategies for protecting the brain rely on the control of physiological variables, anaesthesia, administration of non-anaesthetic pharmacological agents and preconditioning. Avoiding hyperthermia, hyperglycaemia and arterial hypotension are passive neuroprotective measures acknowledged in human beings. The protective effect of anaesthesia, compared to the awake state, is demonstrated in animals but remains to be validated in clinical practice. Laboratory studies investigating pharmacological neuroprotection have shown interesting results but most clinical trials have been disappointing except for a few drugs in specific settings. Preconditioning which results in the induction of some resistance to ischaemia appears as a promising strategy. Up to now, the translation of beneficial experimental results into clinical success is considered an entirely permissible hope but remains an unachieved objective.

Summary

As atelectasis occurs in most patients during general anaesthesia and may be one of the major causes for the development of hypoxaemia and nosocomial pneumonia, its prevention may be considered as an important objective in perioperative management. The major causative mechanisms are the loss of respiratory muscle tone, compression and gas absorption. Vital capacity manoeuvres have been proposed as a means to eliminate atelectasis in the vast majority of patients and restore normal pulmonary gas exchange during general anaesthesia. In this review we describe the pathogenesis of atelectasis in the perioperative period and discuss in the light of recent published investigations the suitability of the vital capacity manoeuvre as a tool during general anaesthesia. Reviewing the current literature, a vital capacity manoeuvre during general anaesthesia may only be useful under specific circumstances when mechanical ventilation with a high inspiratory fraction of oxygen is required or during cardiac surgery at the end of cardiopulmonary bypass to reduce the amount of atelectasis and to maintain adequate gas exchange.

Summary

Reporting systems are becoming more widespread in healthcare. Since they may become mandatory under the pressure of insurance companies and administrative organizations, it is important to begin to go beyond a case-by-case approach and to move to a system where there is a general reflection on the best conditions of development and setting up of such systems in medicine. In this paper, we review existing reporting systems, break down their components, examine how they are constructed and propose some ideas on how to articulate them in a dynamic process in order to improve the validity of the tool as mediator of safety, quality and well-being at work.

Summary

Background and objective: The development of acute renal failure (ARF) in critically ill patients is associated with an increase in hospital mortality. Recently, it was shown that starting renal replacement therapy early and using high-filtrate flow rates can improve the outcome, but this could not be confirmed in later investigations. Studying selected patient subgroups could provide a useful basis for patient selection in future trials evaluating the outcome of renal replacement therapies. We, therefore, investigated the impact of the underlying disease on the outcome of patients with ARF.

Methods: We retrospectively analysed 306 patients with ARF who were treated with renal replacement therapy. Patients were classified according to six initial diagnosis groups: haemorrhagic shock, post-cardiac surgery, post-liver transplantation, trauma, severe sepsis and miscellaneous. Univariate and multivariate multiple logistic regression analysis was used to determine which factors influenced the outcome.

Results: Underlying disease proved to be the only independent risk factor for mortality that was present at intensive care unit (ICU) admission (P = 0.047). Patients with severe sepsis had a significantly higher mortality rate (68%) than ARF patients as a whole (51%) (P = 0.02). Length of stay in the ICU, the use of catecholamines, the delay before ARF onset, and the correlation between APACHE II score and ICU length of stay proved to be additional independent predictors of outcome.

Conclusions: Patient selection and subgroup definition according to the underlying disease could augment the usefulness of future trials evaluating the outcome of ARF.

Summary

Background and objectives: Magnesium sulphate infusion during general anaesthesia reduces anaesthetic consumption and analgesic requirements. The aim of this study was to assess the effects of postoperative magnesium infusion on duration of block, sedation and analgesic consumption after spinal anaesthesia.

Methods: Fifty ASA I–II patients were included in the randomized double blind study. Spinal anaesthesia was performed at L3–4 or L4–5 interspace with 12.5 mg 0.5% heavy bupivacaine, using a 25 G Quincke needle. Patients received a 5 mg kg−1 bolus of magnesium sulphate followed by a 500 mg h−1 infusion or saline in the same volumes for 24 h. Time to first pain, analgesic request, return of motor function, visual analogue pain and sedation scores were evaluated every 4 h during the 24 h postoperative period. The t- and U-tests were used for statistical analyses. Data were expressed as mean ± SD, with P < 0.05 being considered significant.

Results: Vital signs were stable during spinal anaesthesia and postoperative period. When compared to the control group, time to analgesic need was increased and total analgesic consumption was reduced in the magnesium group (meperidine consumption 60.0 ± 73.1 mg control group, 31.8 ± 30.7 mg magnesium group, P = 0.02).

Conclusions: Magnesium sulphate infusion may be used as an adjunct for reducing analgesic consumption after spinal anaesthesia.

Summary

Background and objective: Placement of central venous catheters in patients is associated with several risks including endocardial lesions and dysrhythmias. Correct positioning of central venous catheters in the superior vena cava is essential for immediate use. The objective of a first study was to evaluate the signal quality of an intravascular electrocardiogram (ECG) during position control using a guidewire compared with the customary fluid column-based ECG system, and to assess its efficacy of correct placement of the central venous catheter. A second study tested if dysrhythmias can be avoided by intravascular ECG monitoring during catheter and guidewire advancement.

Methods: The jugular or subclavian vein of 40 patients undergoing heart surgery or who were being treated in the intensive care unit was cannulated. Intravascular ECGs were recorded during position control, and guidewire and water column lead were compared in the same patient with regard to the quality of the ECG reading and P-wave enhancement. In another 40 patients, the guidewire was inserted only 10 cm and the central venous catheter advanced under guidewire ECG control. Correct position of all the central venous catheters was confirmed by chest radiography.

Results: All central venous catheters were correctly positioned in the superior vena cava. For the same catheter position, the P-wave was significantly larger in the guidewire ECG than in the fluid column system. No changes in the quality of the ECG were detected when the guidewire was advanced or withdrawn by 1 cm relative to the catheter tip. Cardiac dysrhythmias were not seen during ECG-monitored advancement of the guidewire.

Conclusions: ECG quality using a guidewire lead is superior to the water column-based system. Furthermore, it is independent from the exact position of the guidewire as related to the tip of the catheter. Using intravascular guidewire ECG during advancement can prevent induction of dysrhythmias.

Summary

The mitochondrial myopathies consist of a heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria leading to involvement of the nervous system and muscles as well as other organ systems. The peculiar genetic characteristics of mitochondrial DNA impart distinctive properties to these disorders. The pathophysiology is presented. The methods employed in making the correct diagnosis, the preoperative patient assessment and correction of metabolic dysfunctions and anaesthetic techniques used, are highlighted. The conditions are briefly reviewed and suggestions are made for the safe anaesthetic management of affected patients.

Summary

Background and objective: To survey French anaesthetic practice regarding acid aspiration prophylaxis and compare it with an earlier survey.

Methods: A confidential questionnaire was sent to all 800 maternity units in France to assess three major topics: (a) drugs used for pharmacological prophylaxis; (b) regional anaesthesia for labour and Caesarean section and (c) techniques used for general anaesthesia and endotracheal intubation.

Results: Two-hundred-and-two units responded. Pharmacological prophylaxis was regularly used for labouring women in 78% of the responding units in 1998 (compared with 63% in 1988, P < 0.05). Antacid drug use before Caesarean section had increased from 75% in 1988 to 97% in 1998 (P < 0.05). General anaesthesia was used for Caesarean section by less than 2% of responding units (vs. 21% in 1988, P < 0.05). In contrast, there was little change in the use of endotracheal intubation for instrumental delivery (53% vs. 50%) or manual removal of the placenta (15% vs. 16%) between 1988 and 1998. The use of cricoid pressure increased significantly during the 10 yr period (50% vs. 88%, P < 0.05) and the technique was correctly described by 80% of the responding units (vs. 50%, P < 0.05). Similarly, the use of succinylcholine increased significantly from 25% (1988) to 47% (1998) (P < 0.05).

Conclusions: There was a significant overall improvement of French practice regarding acid aspiration prophylaxis in obstetrics. However, the complete prophylaxis strategy is still not used in every patient emphasizing the need for continuing medical education.

Summary

Background and objective: Changes in the middle latency auditory evoked response following the administration of opioids have been shown. However, it remains unclear as to whether these changes are due to a direct depressant effect of opioids on the middle latency auditory evoked response itself, or an indirect effect on account of their action in attenuating central nervous system arousal associated with noxious stimuli. By comparing changes in the middle latency auditory evoked response in intubated and non-intubated patients, receiving saline or remifentanil in different doses, this study attempts to answer this question.

Methods: Fifty-four patients were anaesthetized with isoflurane and nitrous oxide (0.9 MAC) and randomized to 1–6 groups. Groups 1–3 received a bolus injection of either saline 0.9%, low-dose remifentanil (1 μg kg−1) or high-dose remifentanil (3 μg kg−1) prior to intubation of the trachea. Groups 4–6 were not intubated following the bolus injection.

Results: Pa and Nb amplitudes of the middle latency auditory evoked response increased by 82% and 79% with intubation in the saline group (P < 0.005) and these changes were not seen in the patients given remifentanil. There was a significant linear trend for the reduction in Pa and Nb amplitude with increasing remifentanil dose (P < 0.05). In the absence of endotracheal intubation remifentanil had no effect on either the amplitudes or latencies of the waves Pa and Nb and there was no effect of dose. For the haemodynamic measurements remifentanil attenuated the pressor response to intubation (P < 0.001) and had a significant dose-related effect (P < 0.001) in the absence of intubation.

Conclusions: We demonstrated an effect of remifentanil on both the middle latency auditory evoked response and haemodynamic changes to endotracheal intubation. For the non-intubated patients there was only an effect of remifentanil on the haemodynamic measurements. This suggests that remifentanil has an effect on the middle latency auditory evoked response in attenuating the arousal associated with intubation of the trachea but has no effect in the absence of a stimulus.