A randomised, controlled, double-blind trial of ultrasound-guided phrenic nerve block to prevent shoulder pain after thoracic surgery.

Moderate to severe ipsilateral shoulder pain is a common complaint following thoracic surgery. In this prospective, parallel-group study at Odense University Hospital, 76 patients (aged > 18 years) scheduled for lobectomy or pneumonectomy were randomised 1:1 using a computer-generated list to receive an ultrasound-guided supraclavicular phrenic nerve block with 10 ml ropivacaine or 10 ml saline (placebo) immediately following surgery. A nerve catheter was subsequently inserted and treatment continued for 3 days. The study drug was pharmaceutically pre-packed in sequentially numbered identical vials assuring that all participants, healthcare providers and data collectors were blinded. The primary outcome was the incidence of unilateral shoulder pain within the first 6 h after surgery. Pain was evaluated using a numeric rating scale. Nine of 38 patients in the ropivacaine group and 26 of 38 patients in the placebo group experienced shoulder pain during the first 6 h after surgery (absolute risk reduction 44% (95% CI 22-67%), relative risk reduction 65% (95% CI 41-80%); p = 0.00009). No major complications, including respiratory compromise or nerve injury, were observed. We conclude that ultrasound-guided supraclavicular phrenic nerve block is an effective technique for reducing the incidence of ipsilateral shoulder pain after thoracic surgery.

Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia.

Central core disease (CCD) of muscle is an inherited myopathy which is closely associated with malignant hyperthermia (MH) in humans. CCD has recently been shown to be tightly linked to the ryanodine receptor gene (RYR1) and mutations in this gene are known to be present in MH. Mutation screening of RYR1 has led to the identification of two previously undescribed mutations in different CCD pedigrees. One of these mutations was also detected in an unrelated MH pedigree whose members are asymptomatic of CCD. The data suggest a model to explain how a single mutation may result in two apparently distinct clinical phenotypes.

Sleep disturbances in critically ill patients in ICU: how much do we know?

Sleep disturbances in the intensive care unit (ICU) seem to lead to development of delirium, prolonged ICU stay, and increased mortality. That is why sufficient sleep is important for good outcome and recovery in critically ill patients. A variety of small studies reveal pathological sleep patterns in critically ill patients including abnormal circadian rhythm, high arousal and awakening index, reduced Slow Wave Sleep, and Rapid Eye Movement sleep. The purpose of this study is to summarise different aspects of sleep-awake disturbances, causes and handling methods in critically ill patients by reviewing the underlying literature. There are no studies of level 1 evidence proving the positive impact of the tested interventions on the critically ill patients' sleep pattern. Thus, disturbed sleep in critically ill patients with all the severe consequences remains an unresolved problem and needs further investigation.

Withholding or withdrawing therapy in Danish regional ICUs: frequency, patient characteristics and decision process.

BACKGROUND: New options for intensive therapy have increased the necessity of considering withholding or withdrawing therapy at intensive care units (ICUs), but the practice varies according to regional and cultural differences. The aim of this study was to investigate the frequency of withholding or withdrawing therapy in two secondary Danish ICUs, to describe the characteristics of patients in whom such decisions were made and to examine the existing documentation of the decision process. METHODS: A retrospective review of hospital records for all patients admitted to two regional Danish ICUs in 2008. The records were searched for all information regarding deliberations or decisions on withholding or withdrawing therapy. RESULTS: Of 1665 patients admitted to the ICUs, 176 patients (10.6%) died; of these, 34 (19.3%) died while still receiving full active therapy, 25 (14.2%) died after therapy was withheld and 117 (66.5%) died after therapy was withdrawn. An additional 88 patients (5.3%) were discharged alive with therapy either withheld or withdrawn. The patients who died had higher severity scores, were older and were more likely to be men than those who were discharged with full therapy. The main reasons for withholding or withdrawing therapy were prognosis for acute illness and the deemed futility of therapy. The median time from admission to a decision on withholding or withdrawing therapy was 1.4 days. CONCLUSION: Withholding or withdrawing therapy is common in Danish ICUs but more research is needed to explore the different aspects of withholding or withdrawing therapy in Danish ICUs.

Clinical variability of possible malignant hyperthermia as revealed by two cases.

Two cases of possible clinical malignant hyperthermia are described. The variability of the clinical symptoms and signs is discussed and the necessity of performing the diagnostic in vitro muscle contracture test is emphasized.

Pathophysiology of malignant hyperthermia.

Malignant hyperthermia (MH) is a pharmacogenetic disease in man and animals. It primarily involves skeletal muscle tissue, but other tissues might be affected to a lesser degree. Calcium homeostasis in muscle cells is upset in susceptible individuals, so that various agents and circumstances can increase the free, ionised intracellular calcium concentration to damaging levels. The primary defect is not known at present, but is believed to involve an abnormally sensitive calcium-induced calcium release mechanism. Thus small, localised increases in calcium concentration releases more calcium so that a vicious cycle is triggered. The increased calcium concentration causes multiple effects in the muscles by stimulating contraction and a hypermetabolic state, clinically observed as rigidity and fever. If demands on the homeostatic mechanisms to lower the calcium concentration become exhausted, and metabolism is insufficient to supply enough phosphocreatine and ATP, membrane potentials cannot be maintained, and permeability of the cell membranes increase. This causes loss of phosphate and H+ as well as K+ and Mg++, and later myoglobin and creatine kinase. Thereby oxidative metabolism is further impeded with formation of lactate as a result. The ensuing acidosis stimulates sympathetic innervation, resulting in tachycardia, high blood pressure, and vasoconstriction. Hyperkalemia causes arrhythmia. Dantrolene inhibits the release of calcium and can halt the process if given before depletion of the energy rich phosphates is too advanced.

[Renal side-effects of intraoperative and postoperative pain treatment with non-steroidal anti-inflammatory drugs]. / Renale sidevirkninger ved per- og postoperativ smertebehandling med ikkesteroide antiinflammatoriske farmaka.

Non-steroidal anti-inflammatory drugs (NSAID) are now commonly used in the treatment of postoperative pain. In normovolaemic conditions, prostaglandins do not seem to play a substantial role in maintaining renal function. However, numerous studies have shown that during activation of vasoconstrictor systems the synthesis of renal prostaglandins counteracts the vasoconstrictor effects and thereby maintains renal function. In animals, renal blood flow and GFR are markedly decreased when an NSAID is administered in the presence of renal hypoperfusion. Major surgery decreases renal function secondary to stimulation of the adrenosympathetic system and the renin-angiotensin system, and it has previously been demonstrated that maintenance of renal blood flow during laparotomy in dogs depends on an intact prostaglandin synthesis. Perioperative effects of NSAIDs are only sparsely investigated in humans, and studies on the effect on renal haemodynamics have not been presented. As in unanaesthetized volunteers, NSAID have been found to decrease the postoperative excretion of water, sodium and potassium. It therefore still remains unclarified whether general anaesthesia and surgery increase the risk of renal side effects of NSAIDs. Because of the potential risk of peri- and postoperative complications that may further deteriorate renal function, NSAIDs should not be used preoperatively, and not in patients in unstable haemodynamic states.

Guidelines for withholding and withdrawing therapy in the ICU: impact on decision-making process and interdisciplinary collaboration.

INTRODUCTION: Interdisciplinary collaboration in end-of-life decision-making is challenging. Guidelines developed within the interdisciplinary team may help to clarify, describe, and obtain consensus on standards for end-of-life decision-making and care. The aim of the study was to develop, implement, and evaluate guidelines for withholding and withdrawing therapy in the intensive care unit. METHODS: An intervention study in two Danish intensive care units, evaluated in a pre-post design by a retrospective hospital record review and a questionnaire survey. The hospital record review included 1,665 patients at baseline (12-month review) and 897 patients after the intervention (6-month review). The questionnaire survey included 273 nurses, intensivists, and primary physicians at baseline and 229 post-intervention. RESULTS: For patients with therapy withdrawn, the median time from admission to first consideration on level of therapy decreased from 1.1 to 0.4 days (p=0.03), and the median time from admission to a withdrawal decision decreased from 3.1 to 1.1 days (p=0.02). Sixty-five percent of the participants who used the guidelines concerning end-of-life decision-making considered them helpful to high or very high extent. No significant changes were found in satisfaction with interdisciplinary collaboration or in withholding or withdrawing decisions being changed or unnecessarily postponed. The healthcare professionals' perception of the care following withdrawal of therapy increased significantly after implementation of the guidelines. CONCLUSIONS: The study indicates that working with guidelines for withholding and withdrawing therapy in the intensive care unit may facilitate improvements in end-of-life decision-making and patient care, but further studies are needed to provide robust evidence.

Efficacy of A-line AEP Monitor as a tool for predicting acceptable tracheal intubation conditions during sevoflurane anaesthesia.

BACKGROUND: It is essential for the clinical anaesthetist to know whether patients are sufficiently anaesthetized to tolerate direct laryngoscopy and endotracheal intubation. Because of the lack of an accurate objective method to determine the level of general anaesthesia, under- or overdosing of anaesthetics may occur. Auditory evoked potential (AEP) is one of several physiological parameters under investigation. We aimed to determine the clinically required depth of anaesthesia, measured by the A-line AEP Monitor and expressed as A-Line ARX Index (AAI) for 90% probability of acceptable conditions for endotracheal intubation. METHODS: We studied 108 patients anaesthetized by mask with increasing concentration of sevoflurane in 30% oxygen and 70% nitrous oxide. Fentanyl 1.5 microg kg(-1) and glycopyrrolate 0.2 mg were administered intravenously immediately before starting induction of anaesthesia. The monitor was programmed to give an alarm at AAI 10, 15, 20, 25 or 30 according to randomization. When the alarm sounded, the end-expiratory sevoflurane concentration was registered and endotracheal intubation was attempted. Intubation conditions were assessed by an observer blinded to the AAI. RESULTS: At AAI 10 we found acceptable conditions in 91% (confidence interval [CI 72-99%]) of patients. The prediction probability value P(K) of AAI was 0.69 (CI 0.59-0.79) and the P(K) of end-expiratory sevoflurane concentration was 0.93 (CI 0.87-0.99). ED(90) (the AAI with a 90% probability of acceptable intubation conditions) was calculated as 8.5 (CI 0-17.5). CONCLUSIONS: AAI indicates the depth of anaesthesia necessary for acceptable endotracheal intubation conditions. Under the conditions of the present study, end-expiratory sevoflurane concentration was a better predictor and may turn out to be more useful in the clinical setting.

Incidence of malignant hyperthermia in Denmark.

Questionnaires were sent to all anesthesia departments in Denmark to determine the total number of anesthetics given per year, and the distribution of different types of anesthesia. All cases of suspected malignant hyperthermia forwarded to the Danish Malignant Hyperthermia Register during a 6.5 yr period were reviewed and divided into subgroups according to clinical criteria. The incidence of suspected malignant hyperthermia in these subgroups was calculated in relation to type of anesthesia. The results are based on information about 386,250 anesthetics and 154 cases of suspected malignant hyperthermia. All cases of malignant hyperthermia occurred during general anesthesia, and more than 75% during anesthesia with a combination of potent inhalation agents and succinylcholine. The incidence of fulminant malignant hyperthermia was low: 1 in 250,000 total anesthetic procedures, but 1 in 62,000 anesthetic procedures with a combination of potent inhalation agents and succinylcholine. Masseter spasm occurred in 1 of 12,000 anesthetic procedures in which succinylcholine was administered. Suspicion of malignant hyperthermia was raised in 1 of 16,000 anesthetics total, but in 1 of 4,200 anesthetics with the above-mentioned combination of agents.

Influence of propranolol on the in vitro response to caffeine and halothane in malignant hyperthermia-susceptible muscle.

In vitro contracture tests for susceptibility to malignant hyperthermia (MH) were performed with halothane and caffeine in 27 patients according to the protocol of the European MH Group. Additional halothane and caffeine tests were performed in the presence of propranolol 80 micrograms/l. Contractures after exposure to halothane were seen only in MH-susceptible (MHS) patients (n = 12), and were not affected by propranolol. In contrast, propranolol shifted the caffeine dose-response curve to the right and significantly increased the caffeine threshold in the MHS group. Propranolol did not influence the caffeine results in the normal response group group (n = 12). It is concluded that beta-blockers should be discontinued before investigation for MH susceptibility.

[Malignant hyperthermia]. / Malign hypertermi.

Malignant hyperthermia (MH) is a life threatening complication following anaesthesia with potent inhalational agents and suxamethonium. The signs of MH are caused by increased metabolism and secondary stimulation of the sympathetic nervous system due to uncontrolled, high intracellular concentrations of calcium in skeletal muscle. The hyperthermia is secondary to the increased energy turnover. Calcium release from the sarcoplasmic reticulum is increased due to a low threshold for release and prolonged opening of the calcium channel upon normal stimulation. The gene encoding the calcium channel is localized on chromosome 19 in humans, and a substitution of cysteine for arginine has recently been described in one family with MH.

Use of vecuronium and doxapram in patients susceptible to malignant hyperthermia.

Neuromuscular blockade was obtained with vecuronium 108 micrograms kg-1 in 44 patients undergoing diagnostic muscle biopsy as part of an investigation of malignant hyperthermia (MH) susceptibility. At the termination of anaesthesia doxapram 1.43 mg kg-1 was given in an attempt to antagonize postoperative respiratory depression. Rectal, muscle and skin temperatures, blood lactate concentration and venous PCO2 were measured before, during and after anaesthesia. Susceptibility to MH was established by in vitro contracture tests according to the protocol of the European MH Group. Twenty patients were susceptible to MH (MHS), 19 were MH non-susceptible (MHN) and five MH equivocal (MHE). No adverse effects of the drugs were observed. There were no differences between the three groups in rectal or muscle temperature, blood lactate concentration or venous PCO2 at any time. Doxapram did not prevent an increase in postoperative PCO2. It is concluded that vecuronium and doxapram may be safely administered to patients susceptible to MH.

Influence of salbutamol on the in vitro muscle response to caffeine and halothane in malignant hyperthermia.

In vitro contracture tests for susceptibility to malignant hyperthermia (MH) were performed with halothane and caffeine in 34 patients, according to the protocol of the European MH Group. Additional halothane and caffeine tests were performed in the presence of salbutamol 50 micrograms/l. Contractures after exposure to halothane were seen only in MH-susceptible (MHS) patients (n = 16), and were not changed by salbutamol. Salbutamol did not influence the caffeine dose-response curves in any of the groups (n = 14 in the MH-non-susceptible (MHN) group). The caffeine threshold concentration was significantly increased by salbutamol in the MHS group.