B-type natriuretic peptide to assess haemodynamic status after cardiac surgery.

BACKGROUND: B-type natriuretic peptide (BNP) is the most powerful hormonal marker of left ventricular dysfunction and could be considered as an indicator of ventricular preload. The aim of this prospective study was to compare the respective value of BNP and cardiac filling pressures to assess the response to volume load after cardiac surgery. METHODS: Thirty-seven mechanically ventilated patients suffering from acute circulatory failure immediately after cardiac surgery, and equipped with a pulmonary-artery catheter were included. All haemodynamic measurements were taken before and after volume expansion using 500 ml of 4% modified fluid gelatin. RESULTS: Fifteen patients were volume responders (CI increase>or=15%) and 22 were non-responders. Right atrial pressure, pulmonary-artery occlusion pressure and BNP before volume loading were not significantly different between the responders and non-responders. BNP concentration before volume infusion significantly correlated to preoperative left ventricular ejection fraction, aortic cross-clamping time, serum creatinine, mean pulmonary arterial pressure and intensive care unit duration whereas no correlation was found with pulmonary-artery occlusion pressure or cardiac index. CONCLUSION: BNP level after cardiac surgery was influenced by many perioperative variables, limiting its usefulness as an indicator of cardiac preload or a predictor of volume responsiveness in this population.

A discrepancy resolved: human satellite cells are not preprogrammed to fast and slow lineages.

Satellite cells from chicken and mouse muscle when differentiated in vitro have been shown to display a myosin heavy chain phenotype that corresponds to the fibre from which they originated. Indirect evidence has suggested that this might not be the case for human satellite cells. In the present study we have compared the myosin heavy chain (MHC) profile expressed by differentiated cultures of satellite cells isolated from single fast or slow muscle fibres. The MHC composition of the isolated fibres was determined by sodium dodecyl sulfate glycerol gel electrophoresis and Western blotting. The MHC profile expressed by the differentiated myotubes was identified by immunostaining using specific antibodies. Our results show that all human satellite cells isolated from either fast or slow fibres form myotubes in vitro which co-express both fast and slow MHCs independently of the fibre type from which they originated. These results confirm that human satellite cells, in contrast to those of birds and rodents, are not confined to distinct fast and slow lineages.

Prolonged heparin administration during clopidogrel treatment in healthy subjects.

The potential pharmacological interaction between clopidogrel and heparin was assessed in a randomized, placebo-controlled study carried out in 12 healthy male subjects. Clopidogrel 75 mg once daily or placebo was given in a randomized fashion for 12 days during two periods separated by a 21-day washout period. Sodium heparin was administered as a prolonged intravenous infusion at a starting dose of 300 IU/kg/24 hours then adjusted so as to maintain the activated partial thromboplastin time (APTT) ratio for subject versus control within the therapeutic range of 1.7 to 2.3 for 4 days from day 9 through day 13 of each period. For each period, the following main parameters were measured: total heparin consumption; APTT on days 1 and 8 to 12 before drug intake and on days 13, 14 and 26; bleeding time and platelet aggregation induced by 5 microM ADP on days 1, 8 to 10 and 12 before drug intake, and on days 14 and 26; APTT measured 3 times on day 9, i.e., before the start of heparin infusion, then 3 and 6 hours later. During day 9 to 13 period, the subject/control APTT ratio remained within the specified 1.7 to 2.3 range with no statistically significant difference between the clopidogrel and placebo treatments. The mean (+/-s.e.m.) volumes of heparin infused in each group were 81384+/-2793 IU and 79867+/-2788 IU in the clopidogrel and placebo groups, respectively. The 90% confidence interval of the mean heparin volume difference fell within the+/-10% interval of the placebo mean centered on zero. Bleeding time in the placebo group remained practically unchanged throughout the study. In the clopidogrel group, bleeding time prolongation factor was significantly increased from baseline to day 9, with clopidogrel alone then remained stable at 1.2 following co-administration of heparin until the end of treatment; hence, it was not modified by the coadministration of heparin. ADP (5 microM)-induced platelet aggregation was inhibited by 27+/-12% after 7 days of clopidogrel administration alone, and no significant further change was observed when heparin was coadministered. There were no adverse events that could be related to clopidogrel. In conclusion, under the study conditions, no interactions between clopidogrel and heparin were observed.

Comparison of the effects of mivacurium on the diaphragm and geniohyoid muscles.

Although subjects often report difficulty with swallowing shortly after receiving neuromuscular blocking agents, difficulty with swallowing during recovery from neuromuscular blocking agents appears to be infrequent. We have used electromyography to compare onset and recovery at the diaphragm and geniohyoid airway muscles after an intubating dose of mivacurium (0.2 mg kg-1) to determine if the geniohyoid muscles were particularly sensitive to neuromuscular blocking agents. Twelve adults undergoing elective surgery were anaesthetized with propofol and fentanyl and the trachea intubated without neuromuscular blocking agents. The left hypoglossal and right phrenic nerves were stimulated with percutaneous needle electrodes and the electromyogram recorded with surface electrodes. EMG responses were measured after a bolus dose of mivacurium 0.2 mg kg-1. Recordings were also made of the mechanical response of the adductor pollicis to supramaximal ulnar nerve stimulation. There was no difference in the rate of onset of block for geniohyoid muscles and the diaphragm, but recovery to 25% and 90% of the control response was shorter at the diaphragm (median 14.5 (95% confidence limits 12.9-15.3) min and 23.8 (21.7-26) min) than at the geniohyoid muscle (19.4 (15.6-20.1) min and 29.2 (26.3-31.4) min), respectively (P < 0.05). When the train-of-four ratio of the mechanical response of the thumb reached 70%, the diaphragm and geniohyoid muscles had recovered completely in all patients.

Comparison of the neuromuscular blocking effect of atracurium and vecuronium on the adductor pollicis and the geniohyoid muscle in humans.

BACKGROUND: Residual paralysis of suprahyoid muscles may occur when the adductor pollicis response has completely recovered after the administration of a neuromuscular blocking agent. The response of the geniohyoid muscle to intubating doses of muscle relaxants is evaluated and compared to that of adductor pollicis. METHODS: Sixteen patients undergoing elective surgery under general anesthesia were given 5-7 mg.kg-1 thiopental and 2 micrograms.kg-1 fentanyl intravenously for induction of anesthesia. Eight (half) patients then received 0.5 mg.kg-1 atracurium, and the other eight received 0.1 mg.kg-1 vecuronium. The evoked response (twitch height, TH) of the adductor pollicis was monitored by measuring the integrated electromyographic response (AP EMG) on one limb and the mechanical response, using a force transducer (AP force), on the other. The activity of geniohyoid muscle (GH EMG) was measured using submental percutaneous electrodes. The following variables were measured: maximal TH depression; onset time for neuromuscular blockade to 50%, 90%, and maximal TH depression (OT50, OT90, and OTmax); times between administration of neuromuscular blocking agent and TH recovery to 10%, 25%, 50%, 75%, and 90% of control; and time for return of train-of-four ratio to return to 0.7. RESULTS: The principal findings were (1) OTmax was significantly (P < 0.01) shorter for geniohyoid than for adductor pollicis after either atracurium or vecuronium (OTmax was 216, 256, and 175 s for AP force, AP EMG, and GH EMG, with atracurium and 181, 199, and 144 s with vecuronium, respectively), and (2) the evoked EMG of geniohyoid recovered at the same speed as the EMG of adductor pollicis after an intubating dose of atracurium or vecuronium (recovery of TH to 75% of control at 50, 48, 42 min with AP force, AP EMG, and GH EMG with atracurium and 46, 45, and 42 min with vecuronium, respectively). CONCLUSIONS: Once the adductor pollicis response has returned to normal values after a single intubating dose of atracurium or vecuronium, the risk of residual depression of the TH of the geniohyoid muscle, one of the principal muscles contributing to airway patency, appears unlikely.

Onset of neuromuscular block is the same if the ipsilateral or contralateral limb to the injection site is used for monitoring.

We studied 40 healthy adult patients undergoing elective surgery who were premedicated with flunitrazepam. Before induction of anaesthesia, one of the upper limbs was cannulated and an i.v. infusion of 0.9% saline commenced. Patients were given fentanyl and thiopentone for induction of anaesthesia and then 50% (20 patients) received atracurium 0.5 mg kg-1 and the other 50% vecuronium 0.1 mg kg-1. Neuromuscular block (maximum degree of depression of the elicited first twitch and the onset time of depression of twitch height to 50%, 90% and 100% of control) and skin temperature (at the thenar eminence) were monitored in both the limb with the i.v. infusion and the non-cannulated upper limb. There was no difference in onset time and degree of neuromuscular block between the two upper limbs. Skin temperature was not significantly different between the two upper limbs. We conclude that each upper limb, irrespective of whether an i.v. infusion is in progress, may be used for monitoring onset of neuromuscular block.

Recovery of the swallowing reflex after propofol anesthesia.

The swallowing reflex is depressed by anesthetics. During recovery from anesthesia the rapid return of laryngeal and upper airway reflexes is important to protect the lower airway from aspiration. This study measures the recovery of the swallowing reflex after propofol anesthesia. Fifteen patients undergoing a colonoscopy under general anesthesia were studied. No premedication was given. Anesthesia was induced with propofol 2 mg/kg followed by an infusion of 10 mg.kg-1.h-1. The swallowing reflex was measured every 3 min after the end of propofol infusion for 30 min. To initiate swallowing, 0.3 mL of distilled water was injected into the pharynx at two different speeds: a slow injection over 3 s, and a bolus injection. The swallowing reflex was determined by measuring the latency period (i.e., time from water injection to start of electromyographic (EMG) activity measured in the glossal muscles). Swallowing activity was determined by integration of the EMG (EMGi) of the glossal muscles during swallowing. The latency periods after slow and bolus injections were significantly increased for the first 12 min after the end of the propofol infusion and returned to control (preanesthetic values) at 24 min. The EMGi was significantly decreased over the first 12 min and returned to control at 21 min. Propofol depresses the swallowing reflex, but complete recovery is rapid. This study suggests that the oral intake could be allowed early after recovery from anesthesia when propofol is used as the sole anesthetic.

Pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis.

BACKGROUND: Rocuronium, like other steroidal nondepolarizing muscle relaxants, may in part be eliminated by the liver. To determine the influence of liver disease on its neuromuscular blocking effect, we studied the pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis. METHODS: Eighteen patients undergoing elective surgery, 10 with cirrhosis and 8 with normal liver function, were studied. Anesthesia was induced with intravenous thiopental 5-7 mg.kg-1 and maintained with 60% nitrous oxide in oxygen and repeated doses of fentanyl 2 micrograms.kg-1. The force of thumb adduction in response to supramaximal ulnar nerve stimulation was monitored and recorded. An intravenous bolus of rocuronium 0.6 mg.kg-1 was administered and venous blood sampled at frequent intervals for 6 h. Plasma concentrations of rocuronium was measured by high-pressure liquid chromatography. Data were fitted to both a pharmacokinetic and a pharmacodynamic model by using a two-compartment open model and an effect compartment model. Data were analyzed by least-squares regression. RESULTS: The onset of neuromuscular blockade was longer (P < 0.01) in patients with cirrhosis (158 +/- 56 s) than in normal patients (108 +/- 33 s). Recovery of the thumb twitch to 75 and 90% of its control value was 77 +/- 25 and 88 +/- 29 min in cirrhotic patients versus 57 +/- 11 and 64 +/- 13 min, respectively, in normal patients (P < 0.05). The central volume of distribution of rocuronium was 104 +/- 21 in cirrhotic patients and 78 +/- 24 ml.kg-1 in normal patients (P < 0.05). No significant difference in elimination kinetics was observed between the two groups. The elimination half-life was 87.5 +/- 17.5 min in normal patients and 96.0 +/- 36.8 min in cirrhotic patients (difference not significant). This increased onset time was linearly correlated to the increased central volume of distribution of rocuronium in cirrhosis. CONCLUSION: Rocuronium onset time is longer in cirrhotic patients than in those with normal liver function; this can be explained by an increase in the volume in which rocuronium initially distributes. Although elimination kinetics are unchanged in patients with cirrhosis, rocuronium recovery time is prolonged in cirrhotic patients.

Midazolam/propofol but not propofol alone reversibly depress the swallowing reflex.

General anaesthetics depress swallowing and this is a reason to delay oral intake after general anaesthesia. The swallowing reflex was studied 2 h after general anaesthesia for patients undergoing colonoscopy. Forty-one patients were anaesthetized with midazolam 75 micrograms.kg-1 followed by a continuous infusion of propofol and 39 patients with propofol 1.5 mg.kg-1 bolus followed by an infusion. Swallowing reflex was measured by electromyography 2 h after induction of anaesthesia, before and 5 min after the administration of flumazenil (0.2 mg) or placebo. Two h after anaesthesia, the state of consciousness was almost normal in all patients and did not change after flumazenil. At two hours, the latency times for the swallowing reflex in patients treated with propofol alone were of 1.4 +/- 0.4 s and were significantly shorter (P < 0.05) than the value of 1.9 +/- 0.8 s observed in patients who received midazolam with propofol. In the latter group the latency time of the swallowing reflex was significantly reduced following the administration of flumazenil but not placebo. In patients who received propofol without midazolam, the administration of flumazenil or placebo was not associated with significant changes in the latency times. There were also no significant differences in the latency times in the subgroup that received midazolam followed by flumazenil and the propofol alone groups that did or did not receive flumazenil. These results suggest that midazolam still exerts a depressive effect on the swallowing reflex 2 h after its administration despite the recovery of normal consciousness.

[Diprivan: sedation for difficult intubation]. / Diprivan: sédation pour intubation difficile.

No study has compared anaesthetic protocols appropriate for the sedation for fiberoptic tracheal intubation. Extrapolation of results of randomised studies comparing sedation techniques for diagnostic bronchoscopy under local anaesthesia enables the following conclusions: 1. Possible hypnotic agents for this procedure are benzodiazepines, barbiturates and propofol. Fentanyl improves the conditions for bronchoscopy. 2. Sedation using propofol is a well established technique. The induction dose, given as a bolus injection is 1 mg.kg-1, followed by continuous maintenance infusion of 1 mg.kg.h-1. 3. Irrespective of the sedation protocol used, there is always respiratory depression which justifies the need for preoxygenation, continuous oxygenation and Spo2 monitoring. Reversal of benzodiazepine and opioid effects may temporarily protect against respiratory depression.

Pharmacokinetics and pharmacodynamics of pipecuronium in patients with cirrhosis.

To determine the effect of liver cirrhosis on the pharmacokinetics and pharmacodynamics of pipecuronium, the authors administered 100 micrograms/kg of pipecuronium intravenously to eight patients with liver cirrhosis and eight patients with normal liver and renal function undergoing elective abdominal surgery. All patients were anesthetized with thiopental (5-7 mg/kg), nitrous oxide (50-70% in oxygen), and fentanyl in repeated doses (2 micrograms/kg). Plasma concentrations of pipecuronium were determined by high-pressure liquid chromatography. A two-compartment open model was used for pharmacokinetic analysis. Thumb-elicited mechanical response to single-twitch ulnar nerve stimulation was also measured. Total plasma clearance did not differ between controls (2.96 +/- 1.05 mL.min-1.kg-1, mean +/- SD) and cirrhotics (2.61 +/- 1.16 mL.min-1.kg-1). Terminal elimination half-life was 111 +/- 46 min in controls and 143 +/- 25 min in cirrhotics. The total apparent volume of distribution at steady state did not differ between controls (350 +/- 81 mL/kg) and cirrhotics (452 +/- 222 mL/kg). The volume of the central compartment was not different between the two groups. The onset of neuromuscular blocking effect was longer in cirrhotics (233 +/- 112 s) (P < 0.05) than in controls (170 +/- 33 s). The clinical duration (injection until single twitch returned to 25%) was similar between the two groups: 167 +/- 41 min in controls and 165 +/- 48 min in cirrhotics. The authors conclude that hepatic insufficiency due to cirrhosis does not alter the pharmacokinetics and pharmacodynamics of pipecuronium (100 micrograms/kg).

Partial reversal of the effects of extradural clonidine by oral yohimbine in postoperative patients.

Extradural clonidine produces analgesia, with sedation, hypotension and bradycardia, in postoperative patients. This study assessed if oral yohimbine would reverse these side effects. We studied 30 ASA I-II patients undergoing orthopaedic surgery. After operation they were allocated randomly to three groups to receive placebo, extradural clonidine 450 micrograms or extradural clonidine 450 micrograms plus oral yohimbine 16 mg. Pain score was measured on a visual analogue scale (VAS); sedation was assessed on a simple scale graded from 0 (awake and alert) to 3 (deeply sedated, awakening after tactile stimulations) and heart rate and arterial pressure were monitored for 5 h. Yohimbine reversed the sedation induced by extradural clonidine, but also shortened the duration of analgesia (31 (SD 15) min, 186 (72) min and 126 (52) min in the placebo, extradural clonidine and extradural clonidine+yohimbine groups, respectively) (P < 0.05), and did not reduce the hypotension and bradycardia related to clonidine administration. These results suggest that alpha 2 adrenoceptors are mediators of the sedation induced by clonidine and that the haemodynamic effects are not related to stimulation of supraspinal alpha 2 receptors.

Priming doses of atracurium and vecuronium depress swallowing in humans.

The administration of low doses of muscle relaxant may cause peripheral muscular weakness including difficulty in swallowing. In the present study, the effect of priming doses of atracurium and vecuronium on swallowing was studied. Sixty patients undergoing elective surgery under general anesthesia were divided randomly into four groups of 15 patients and received as a priming dose either vecuronium (10 or 15 micrograms/kg) or atracurium (50 or 75 micrograms/kg). Swallowing muscle activity was measured by electromyography using submental surface electrodes. Swallowing was initiated by administration of 0.3 ml distilled water through an oral catheter. Swallowing reflex was determined by measuring the latency time (i.e., time from water administration to start of EMG activity of glossal muscles). Swallowing activity was determined by integration of the EMG of glossal muscles during swallowing. Peripheral muscle strength was determined by hand grip strength. Swallowing reflex activity and peripheral muscle strength were measured before and 3 and 6 min after administration of vecuronium or atracurium. Latency time remained unchanged after any of the priming doses. Integrated EMG decreased significantly (P < .001) 3 and 6 min after all priming doses tested (42-75% of baseline value). Only after atracurium 75 micrograms/kg was the hand grip strength significantly decreased (P < .01). These results suggest that owing to its effect on swallowing, the priming dose should be used with caution.