No abstract

Thoracotomy is often responsible for chronic pain, possibly of neuropathic origin. To confirm preclinical studies, the preventive effects of perioperative ketamine were tested in a randomized, double-blind, placebo-controlled clinical trial on persistent neuropathic pain after thoracotomy. Eighty-six patients scheduled for thoracotomy under standardised general anaesthesia were randomised to receive either ketamine (1 mg kg(-1) at the induction, 1 mg kg(-1) h(-1) during surgery, then 1 mg kg(-1) during 24 h; n=42) or normal saline (n=44). Postoperative analgesia included a single dose of intrapleural ropivacaine, intravenous paracetamol and nefopam, and patient-controlled intravenous morphine. Vital parameters and analgesia were recorded during the 48 first postoperative hours. Seventy-three patients were followed up. The patient's chest was examined 1-2 weeks, 6 weeks and 4 months after surgery. At the last two observations, spontaneous pain score over a one-week period (visual analogue scale), neuropathic pain score (NPSI), and intake of analgesics, were assessed. No drug affecting neuropathic pain (except opiates) was given during the follow-up. Two patients in each group were lost to follow-up after the 6 week visit. Ketamine improved immediate postoperative pain, but the groups were similar in terms of neuropathic pain and intake of analgesics, 6 weeks (NPSI score: ketamine: 1.25 [0-4.125]; placebo: 1 [0-4]) and 4 months after surgery. Thus, ketamine given in 24-h infusion failed to prevent chronic neuropathic pain after thoracotomy. Other perioperative preventive long-lasting treatments or techniques could be tested in this context.

SummaryWe compared the duration of analgesia produced by a mixture of lignocaine and bupivacaine, either alone or combined with morphine (75 mg.kg ¹1 ), buprenorphine (3 mg.kg ¹1 ) or sufentanil (0.2 mg.kg ¹1 ) in 80 patients after brachial plexus block for orthopaedic surgery of the upper limb. The characteristics of analgesia were evaluated hourly using a visual analogue scale. The analgesia was considered satisfactory for scores of 30 or less. The median duration (range) of satisfactory analgesia was: 11.5 (8-15) h without an opioid, 21 (9-27) h with morphine, 20 (14-34) h with buprenorphine and 24.5 (11-38) h with sufentanil. We conclude that the addition of an opioid to a local anaesthetic mixture lengthens the duration of analgesia. The demonstration that opioid receptors are present in the peripheral nervous system [1] prompted recent investigations of the effects of using opioids, alone or combined with local anaesthetics, for regional analgesia procedures like brachial plexus block. Several authors have investigated the efficacy of injecting opioids into the brachial plexus sheath [2][3][4][5][6][7][8][9][10][11][12][13][14], but the results remain inconclusive. Some authors did not observe any benefit from adding opioids [6,7,[9][10][11], but the drugs and doses of opioids and local anaesthetics and the populations of patients, were different in the various studies. Lipid solubility and the affinity of the different opioids for their receptors seemed to be important factors [1]. The aim of this study was to evaluate the effects of different opioids which have either different receptor affinities or different lipid solubilities in patients scheduled for osteosynthesis of a fractured upper limb, without any signs of inflammation. For this purpose, we compared the quality and the duration of the analgesia produced by a brachial plexus block with a mixture of lignocaine and bupivacaine, either alone or combined with morphine, buprenorphine or sufentanil. MethodsThe study was approved by our local ethics committee and informed consent was obtained from the 89 participating ASA grade 1 or 2 patients who were less than 65 years old. They were scheduled to undergo osteosynthesis of the upper limb under brachial plexus anaesthesia. After oral medication with hydroxyzine 100 mg given 2 h before surgery, the brachial plexus block was performed with the aid of a nerve stimulator, using the supraclavicular technique. The patients were randomly allocated into four groups: the control group (group C), which was given a mixture of 1 mg.kg ¹1 of bupivacaine 0.5% and 2 mg.kg ¹1of lignocaine 1% with 1 : 200 000 adrenaline and groups M, B and S, which were all given the same mixture, combined with either morphine 75 mg.kg ¹1 , buprenorphine 3 mg.kg ¹1 or sufentanil 0.2 mg.kg ¹1 . The opioids were diluted in the bupivacaine, in order to obtain the same volume per kilogram in all the groups. In all cases, there was an interval of more than 45 min between the injection of the anaesthetic solution and the surgical procedure.

The cellular mechanisms responsible for enhanced muscle protein breakdown in hospitalized patients, which frequently results in lean body wasting, are unknown. To determine whether the lysosomal, Ca2+-activated, and ubiquitin-proteasome proteolytic pathways are activated, we measured mRNA levels for components of these processes in muscle biopsies from severe head trauma patients. These patients exhibited negative nitrogen balance and increased rates of whole-body protein breakdown (assessed by ['3C]leucine infusion) and of myofibrillar protein breakdown (assessed by 3-methylhistidine urinary excretion). Increased muscle mRNA levels for cathepsin D, m-calpain, and critical components of the ubiquitin proteolytic pathway (i.e., ubiquitin, the 14-kDa ubiquitin-conjugating enzyme E2, and proteasome subunits) paralleled these metabolic adaptations. The data clearly support a role for multiple proteolytic processes in increased muscle proteolysis. The ubiquitin proteolytic pathway could be activated by altered glucocorticoid production and/or increased circulating levels of interleukin 1p and interleukin 6 observed in head trauma patients and account for the breakdown of myofibrillar proteins, as was recently reported in animal studies.Many intensive care patients experience a rapid loss of body proteins. Tracer studies have shown, in burned (1) or septic (2) patients, increased whole-body protein breakdown. Elevated muscle proteolysis is largely responsible for this increase, as shown by enhanced urinary 3-methylhistidine excretion, an index of myofibrillar protein breakdown (3). However, none of the methods to measure proteolysis in vivo, namely, whole body tracer studies, 3-methylhistidine excretion, or tracer balance across the forearm (a method allowing direct measurement of muscle proteolysis) (4), gives any information on the cellular mechanisms responsible for increased muscle proteolysis.There are three well characterized intracellular proteolytic systems in mammalian skeletal muscle. The lysosomal pathway, which mostly degrades soluble and extracellular proteins, is not involved in the degradation of myofibrillar proteins (5-7) and contributes little to overall protein breakdown in muscles incubated under optimal conditions (7-9). The Ca2+-dependent proteinases (calpains) degrade cytoskeletal but not myofibrillar proteins (5-7) and are mostly involved in limited proteolysis of some specific target proteins (10). The third, and most recently identified system, is the ATP-ubiquitindependent pathway in which proteins to be degraded are first covalently linked to multiple ubiquitin chains in a several-step process requiring ATP, the ubiquitin-activating enzyme El,The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.and one of the ubiquitin-conjugating enzymes (E2). One of the ubiquitin protein ligases (E3) is sometimes required for substrate recognit...

The effect of trauma on protein metabolism was investigated in the whole body, muscle, and liver in severely head-injured patients presenting an acute inflammatory response by comparison to fed control subjects receiving a similar diet. Nonoxidative leucine disposal (an index of whole body protein synthesis) and muscle, albumin, and fibrinogen synthesis were determined by means of a primed, continuous infusion ofl-[1-13C]leucine. Nonoxidative leucine disposal increased by 28% in the patients ( P < 0.02). Fractional muscle protein synthesis rate decreased by 50% ( P < 0.01) after injury. Fractional and absolute fribrinogen synthesis rates were multiplied by two and nine, respectively, after injury ( P< 0.001). Albumin levels were lower in patients (25.2 ± 1.2 g/l, means ± SE) than in controls (33.7 ± 1.2 g/l, P < 0.001). However, fractional albumin synthesis rates were increased by 60% in patients (11.4 ± 1.0%/day) compared with controls (7.3 ± 0.4%/day, P < 0.01). Therefore, 1) head trauma induces opposite and large changes of protein synthesis in muscle and acute-phase hepatic proteins, probably mediated by cytokines, glucocorticoids, and other stress hormones, and 2) in these patients, hypoalbuminemia is not due to a depressed albumin synthesis.

In an acute care setting, a high level of education was a key factor for high job stress and was associated with a perception of a low control in the workplace, both of which may be predictors of adverse mental health. In particular, the lack of control has been associated with moral distress, a frequently reported characteristic of acute care settings. To enhance the personal and professional outcomes of the advanced registered nurses, strategies for supporting nurses manage daily stressors in acute care are urgently required.

Fentanyl kinetics were studied in patients with cirrhosis and in patients with normal hepatic and renal function undergoing surgery under general anaesthesia, the latter group served as the controls. Plasma fentanyl concentrations declined bi-exponentially in the controls with an average elimination half-life (T1/2 beta) of 263 min; total plasma clearance (Cl) as 10.8 ml min-1 kg-1, and total apparent volume of distribution (V beta) 3.81 litre kg-1. No significant change was observed in patients with cirrhosis: T1/2 beta was 304 min, Cl 11.3 ml min-1 kg-1 and V beta 4.41 litre kg-1. These data suggest that the elimination half-life of fentanyl is not primarily influenced by the rate at which it is metabolized in the liver.

The ED protocol was more effective than the i.t. protocol, whilst side-effects were similar.