Effects of an opioid on respiratory movements and expiratory activity in humans during isoflurane anaesthesia.

Opioids increase abdominal muscle activity during anaesthesia. We proposed that opioid activity during anaesthesia would change chest wall size and movement, and contribute to ventilation. Using an optical system to measure chest wall volume, we studied 10 patients during isoflurane anaesthesia, first under the influence of an opioid and then after reversal with naloxone. Measurements were made during quiet breathing and with carbon dioxide stimulation. Airway occlusion pressure was measured to assess inspiratory and expiratory muscle activity. Chest wall volume decreased with the onset of spontaneous breathing, and decreased further when breathing was stimulated by carbon dioxide. Reversal of opioid activity increased chest wall volume. Breathing movements were predominantly abdominal. Opioid action affected the timing and amplitude of breathing but the pattern of abdominal movement was not affected. Since opioids augment abdominal muscle action during expiration, the unchanged pattern of movement can be attributed to both diaphragm and abdominal activity displacing the abdominal wall reciprocally, in the inspiratory and expiratory phases of the respiratory cycle, respectively.

Sugammadex in anesthesia practice.

IMPORTANCE OF THE FIELD: Neuromuscular blocking agents are currently used during anesthesia but put patients at risk of postoperative paralysis. If the residual neuromuscular blockade is not reversed properly at the end of anesthesia, there is a risk of hypoxemia and pulmonary complication. Sugammadex is able to fully reverse different degrees of neuromuscular blockade induced by steroidal neuromuscular blocking agents. AREAS COVERED IN THIS REVIEW: This review provides a background to the use of neuromuscular blocking agents during anesthesia. It also describes the mechanism of reversal and the clinical efficacy of sugammadex, and discusses the future changes in clinical anesthesia induced by this new selective binding agent. WHAT THE READER WILL GAIN: An understanding of the rationale and use of sugammadex as a reversal agent of different degrees of neuromuscular blockade and the use of the high-dose rocuronium-sugammadex combination as an alternative to succinylcholine for rapid sequence induction. TAKE HOME MESSAGE: Sugammadex provides an original mechanism of reversing the effect of neuromuscular steroidal agent by direct inactivation in plasma. Although its effect is spectacular, it is questionable whether this drug will change current practice.

A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia.

BACKGROUND: Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium. METHODS: We designed this randomized, open-label, dose-response trial to explore the dose-response relationship of sugammadex for the reversal of deep neuromuscular blockade induced by rocuronium or vecuronium under propofol-induced and sevoflurane-maintained anesthesia. As a secondary objective, the safety variables of sugammadex were evaluated. After anesthesia induction with propofol, 102 patients aged > or = 20 and < 65 yr were randomized to receive a single bolus dose of rocuronium 0.9 mg/kg (n = 50) or vecuronium 0.1 mg/kg (n = 52), followed by maintenance doses (rocuronium 0.1-0.2 mg/kg or vecuronium 0.02-0.03 mg/kg) as needed. Neuromuscular blockade was monitored using acceleromyography. After the last dose of NMBD, at 1-2 posttetanic counts, a single bolus dose of sugammadex 0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg was administered. The primary efficacy variable was time from start of sugammadex administration to recovery of the T(4)/T(1) ratio to 0.9. RESULTS: The per-protocol population consisted of 48 patients in the rocuronium group and 47 in the vecuronium group. A dose-response effect was demonstrated for decreased mean time to recovery of the T(4)/T(1) ratio to 0.9 with increasing sugammadex dose in both NMBD groups (per-protocol population): rocuronium group, 79.8 (SD 33.0) min (sugammadex 0.5 mg/kg) to 1.7 (0.7) min (4.0 mg/kg) and 1.1 (0.3) min (8.0 mg/kg subgroup); vecuronium group, 68.4 (31.9) min (0.5 mg/kg) to 3.3 (3.5) min (4.0 mg/kg), and 1.7 (0.8) min (8.0 mg/kg subgroup). Neuromuscular monitoring showed recurrent neuromuscular blockade in 5 patients, all in the rocuronium group (2 given sugammadex 0.5 mg/kg and 3 given 1.0 mg/kg), but there were no clinical events attributable to recurrent or residual neuromuscular blockade. CONCLUSION: Sugammadex at doses of > or = 4 mg/kg provides rapid reversal of deep rocuronium- and vecuronium-induced neuromuscular blockade under sevoflurane maintenance anesthesia.

Resistance to D-tubocurarine of the rat diaphragm as compared to a limb muscle: influence of quantal transmitter release and nicotinic acetylcholine receptors.

BACKGROUND: The diaphragm is resistant to competitive neuromuscular blocking agents, as compared to peripheral muscles. The basis of this difference may be a higher concentration of acetylcholine released or higher number of postsynaptic nicotinic acetylcholine receptors in diaphragmatic neuromuscular junctions. METHODS: Nerve-evoked twitch-tension was measured in rat hemidiaphragm as was Extensor digitorum longus (EDL) nerve-muscle preparation to determine the effective D-tubocurarine concentration that decreased twitch responses by 50%. The mean quantal content of endplate potentials was determined in single junctions in a low-Ca(2+), high-Mg(2+) Krebs-Ringer medium. Strips of hemidiaphragm and EDL muscle, containing the endplate regions, were used to determine the number of nAChR nicotinic acetylcholine receptor binding sites with the aid of radiolabeled [(125)I]alpha-bungarotoxin. RESULTS: The effective D-tubocurarine concentration that decreased twitch responses by 50% (median [interquartile range]) was seven-fold higher in the hemidiaphragm than in the EDL (1.82 microm [1.43-2.20] vs. 0.26 microm [0.23-0.29], P < 0.01). The median of the mean quantal content was higher in the hemidiaphragm than in the EDL (0.57 [0.44-0.84] vs. (0.14 [0.11-0.19], P < 0.01). The number of specific [(125)I]alpha-bungarotoxin binding sites to junctional nicotinic acetylcholine receptors was higher in the diaphragm than in the EDL (1.15 fmol/mg [0.48-1.70] vs. 0.55 fmol/mg [0.23-0.70 ], P < 0.05). CONCLUSION: The current study indicates that the resistance of the diaphragm to neuromuscular blocking agents can be explained by both a higher mean quantal content of endplate potentials and a higher number of nicotinic acetylcholine receptor binding sites than in the peripheral EDL muscle.

Noninvasive investigation of autonomic activity after carotid stenting or carotid endarterectomy.

OBJECTIVE: Carotid artery stenting (CAS) has been introduced as an alternative to carotid endarterectomy (CEA) for the treatment of carotid artery stenosis. Both techniques seem to be associated with postoperative hemodynamic lability. Both may induce baroreceptor dysfunction, possibly leading to transient impairment of cardiovascular autonomic activity and resulting in hemodynamic instability. This instability might contribute to postoperative morbidity. To elucidate these phenomena, we studied the cardiac baroreflex and autonomic cardiovascular control after CAS and CEA. METHOD: In 20 patients scheduled for CAS (n = 10) or CEA (n = 10), intra-arterial pressures and electrocardiograms were recorded during 10 minutes before and 8 and 24 hours after the procedure. Spontaneous cardiac baroreflex sensitivity was assessed using the sequence method and cross-spectral analysis. In addition, cardiovascular autonomic activity was investigated using spectral analysis of heart rate variability and systolic arterial pressure variability. RESULTS: After CAS, we demonstrated an increase of the spontaneous baroreflex sensitivity median (interquartile range) from 5.6 (5.1 to 6.2) ms/mm Hg before the procedure to 8.8 (6.8 to 10.5) ms/mm Hg and 7.7 (3.9 to 8.6) ms/mm Hg (P < .001), 8 and 24 hours after the procedure. This was consistent with the increase of the high frequency component of heart rate variability reflecting cardiac parasympathetic activity and a decrease of the low frequency of systolic arterial pressure variability reflecting sympathetic vascular activity. The postoperative period was also associated with decreased systolic arterial pressure from 173 (162 to 190) mm Hg at baseline to 122 (109 to 143) mm Hg and 136 (121 to 143) mm Hg at 8 and 24 hours after CAS (P < .001). No changes in baroreflex sensitivity or in autonomic activity were observed after CEA. CONCLUSIONS: These preliminary data suggest that CAS is associated with parasympathetic predominance postoperatively and may probably explain the lower systolic arterial pressure observed after CAS.

Pressure-volume curves with and without muscle paralysis in acute respiratory distress syndrome.

OBJECTIVE: Pressure-volume (PV) curves are recorded after induction of complete muscle paralysis, which may limit their clinical use. The feasibility of recording PV curves without paralysis has not been tested. In 19 patients with acute respiratory distress syndrome (ARDS) and no hemodynamic instability we prospectively evaluated whether PV curves can be safely and reliably recorded under deep sedation without neuromuscular blockade. METHODS: After standardized sedation (continuous infusion of midazolam and fentanyl) PV curves were recorded during apneic sedation, defined as absence of respiratory effort during a 6-s expiratory pause and during paralysis induced by cis-atracurium. MEASUREMENTS AND RESULTS: Agreement between PV curve parameters in the two conditions was evaluated. Curves were obtained from 10 cmH2O and from zero end-expiratory pressure in all patients under apneic sedation. In five patients propofol was given in addition to midazolam and fentanyl, and in two of them fluid resuscitation was needed. A strong agreement was found for respiratory system compliance and the lower inflection point and for chest wall compliance in the five patients whose esophageal pressure was measured. The variability of the measurements, however, should be taken into account in clinical practice. CONCLUSION: Neuromuscular blockade can be dispensed with when recording PV curves in many ARDS patients. Reliable PV curves can be obtained under anesthesia alone, with no serious adverse effects.

Constant flow insufflation of oxygen as the sole mode of ventilation during out-of-hospital cardiac arrest.

BACKGROUND: Constant flow insufflation of oxygen (CFIO) through a Boussignac multichannel endotracheal tube has been reported to be an efficient ventilatory method during chest massage for cardiac arrest. METHODS: Patients resuscitated for out-of-hospital cardiac arrest were randomly assigned to standard endotracheal intubation and mechanical ventilation (MV; n =457) or use of CFIO at a flow rate of 15 l/min (n=487). Continuous chest compressions were similar in the two groups. Pulse oximetry level was recorded every 5[Symbol: see text]min. Outcome of initial resuscitation, hospital admission, complications, and discharge from the intensive care unit (ICU) were analyzed. The randomization scheme was changed during the study, but the in-depth analysis was performed only on the first cohort of 341 patients with CFIO and 355 with MV, because of randomization problems in the second part. RESULTS: No difference in outcome was noted regarding return to spontaneous circulation (CFIO 21%, MV 20%), hospital admission (CFIO 17%, MV 16%), or ICU discharge (CFIO 2.4%, MV 2.3%). The level of detectable pulse saturation and the proportion of patients with saturation above 70% were higher with CFIO. Ten patients with MV but only one with CFIO had rib fractures. CONCLUSIONS: CFIO is a simplified alternative to MV, with favorable effects regarding oxygenation and fewer complications, as observed in this group of patients with desperate prognosis.

Cholinesterases and the resistance of the mouse diaphragm to the effect of tubocurarine.

BACKGROUND: The diaphragm is resistant to competitive neuromuscular blocking agents. Because of the competitive mechanism of action of tubocurarine, the rate of hydrolysis of acetylcholine at the neuromuscular junction may modulate its neuromuscular blocking effect. The authors compared the neuromuscular blocking effect of tubocurarine on isolated diaphragm and extensor digitorum longus (EDL) muscles and quantified the acetylcholinesterase activity in hetero-oligomers. METHODS: Adult Swiss-Webster and collagen Q-deficient (ColQ) mice were used. The blocking effect of tubocurarine on nerve-evoked muscle twitches was determined in isolated diaphragm and EDL muscles, after inhibition of acetylcholinesterase by fasciculin-1, butyrylcholinesterase by tetraisopropylpyro-phosphoramide, or both acetylcholinesterase and butyrylcholinesterase by neostigmine, and in acetylcholinesterase-deficient ColQ muscles. The different acetylcholinesterase oligomers extracted from diaphragm and EDL muscles were quantified in sucrose gradient. RESULTS: The EC50 for tubocurarine to decrease the nerve-evoked twitch response was four times higher in the diaphragm than in the EDL. The activity of the different acetylcholinesterase oligomers was lower in the diaphragm as compared with the EDL. Inhibition of acetylcholinesterase by antagonists resulted in an increased dose of tubocurarine but an unchanged resistance ratio between the diaphragm and the EDL. A similar diaphragmatic resistance was found in ColQ muscles. CONCLUSION: The current study indicates that, despite differences in acetylcholinesterase activity between the diaphragm and EDL, the diaphragmatic resistance to tubocurarine cannot be explained by the different rate of acetylcholine hydrolysis in the synaptic cleft.

Cardiac troponin I assessment and late cardiac complications after carotid stenting or endarterectomy.

PURPOSE: When compared with carotid endarterectomy (CEA), percutaneous carotid angioplasty with stent replacement (CAS) is a less invasive technique in the treatment of carotid stenosis. However, periprocedural hemodynamic instability still remains a challenge. This instability might lead to myocardial damage, which is now measured accurately by using cardiac troponin I (CTnI). METHODS: This study was designed to compare the periprocedural variation of CTnI in 150 consecutive patients scheduled to undergo CEA (n = 75) or CAS (n = 75). The levels of CTnI were measured until the third postoperative day in all patients. Short-term (1 month) and long-term (up to 5 years) postoperative cardiac outcome were assessed by means of chart review, regular follow-ups, and telephone calls. RESULTS: There was not any statistically significant difference between the 2 groups regarding the demographic characteristics and preprocedural medical status. The incidence of increase of CTnI (>0.5 ng/mL) was significantly higher in the CEA group (13%) compared with that in the CAS group (1%; P = .001). During the acute postprocedural period, the CAS group was significantly more prone to hypotension, requiring vasopressor therapy, whereas the CEA group had more hypertension, necessitating hypotensive medications (P < .001). At 5 years, the overall incidence of major cardiac complications (nonfatal myocardial infarction and death related to cardiac origin) was significantly more frequent in the CEA group (20% vs 5%, P < .01). CONCLUSION: The results of our study suggest that CAS yielded less myocardial damage in the short and long term when compared with CEA. Larger randomized multicenter trials with long-term outcomes are necessary to confirm our findings.

The cytosolic phospholipase A2 pathway, a safeguard of beta2-adrenergic cardiac effects in rat.

We have recently demonstrated that in human heart, beta2-adrenergic receptors (beta2-ARs) are biochemically coupled not only to the classical adenylyl cyclase (AC) pathway but also to the cytosolic phospholipase A2 (cPLA2) pathway (Pavoine, C., Behforouz, N., Gauthier, C., Le Gouvello, S., Roudot-Thoraval, F., Martin, C. R., Pawlak, A., Feral, C., Defer, N., Houel, R., Magne, S., Amadou, A., Loisance, D., Duvaldestin, P., and Pecker, F. (2003) Mol. Pharmacol. 64, 1117-1125). In this study, using Fura-2-loaded cardiomyocytes isolated from adult rats, we showed that stimulation of beta2-ARs triggered an increase in the amplitude of electrically stimulated [Ca2+]i transients and contractions. This effect was abolished with the PKA inhibitor, H89, but greatly enhanced upon addition of the selective cPLA2 inhibitor, AACOCF3. The beta2-AR/cPLA2 inhibitory pathway involved G(i) and MSK1. Potentiation of beta2-AR/AC/PKA-induced Ca2+ responses by AACOCF3 did not rely on the enhancement of AC activity but was associated with eNOS phosphorylation (Ser1177) and L-NAME-sensitive NO production. This was correlated with PKA-dependent phosphorylation of PLB (Ser16). The constraint exerted by the beta2-AR/cPLA2 pathway on the beta2-AR/AC/PKA-induced Ca2+ responses required integrity of caveolar structures and was impaired by Filipin III treatment. Immunoblot analyses demonstrated zinterol-induced translocation of cPLA and its cosedimentation with MSK1, eNOS, PLB, and sarcoplasmic reticulum Ca2+ pump (SERCA) 2a in a low density caveolin-3-enriched membrane fraction. This inferred the gathering of beta2-AR signaling effectors around caveolae/sarcoplasmic reticulum (SR) functional platforms. Taken together, these data highlight cPLA as a cardiac beta2-AR signaling pathway that limits beta2-AR/AC/PKA-induced Ca2+ responses in adult rat cardiomyocytes through the impairment of eNOS activation and PLB phosphorylation.

Hemodynamic effects of portal triad clamping with and without pneumoperitoneum: an echocardiographic study.

The decrease of cardiac index observed during portal triad clamping (PTC) with and without pneumoperitoneum has been studied only with right heart catheterization. To better understand this decrease of cardiac index, we investigated the balance between the adequacy of preload and the ability of the heart to pump against an increased afterload, by using transesophageal echocardiography. Ten patients with PTC performed during laparoscopy and 10 with PTC performed during laparotomy were studied. Five minutes after PTC, the stroke volume, the left ventricular (LV) fractional area change (FAC), and the LV end-systolic wall stress (LVESWS) were measured as the conventional hemodynamic variables. Regional wall motion abnormalities (RWMA) were also recorded. In the laparotomy group, LV end-diastolic area decreased, and LVESWS did not increase significantly. FAC remained stable, and one patient developed RWMA. In the laparoscopic group, LV end-diastolic area remained stable, and LVESWS increased. FAC decreased significantly, and five patients developed RWMA. A decrease in preload was the main important change in the laparotomy group, and in the laparoscopic group a decrease in LV function was demonstrated that was likely a consequence of decreased LV preload and increased LV afterload. However, these did not necessitate stopping the procedure or releasing PTC in these study patients without cardiac disease.

Comparative effect of intraoperative propacetamol versus placebo on morphine consumption after elective reduction mammoplasty under remifentanil-based anesthesia: a randomized control trial [ISRCTN71723173].

BACKGROUND: Postoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect. However, the effect of propacetamol administered intra-operatively on post-operative pain and early postoperative morphine consumption has not been clearly evaluated. In order to evaluate the effectiveness of analgesic protocols in the management of post-operative pain, a standardized anesthesia protocol without long-acting opioids is crucial. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain. METHODS: We were interested in determining the postoperative effect of propacetamol administered intraoperatively after intraoperative remifentanil. Thirty-six adult women undergoing mammoplasty with remifentanil-based anesthesia were randomly assigned to receive propacetamol 2 g or placebo one hour before the end of surgery. After remifentanil interruption and tracheal extubation in recovery room, pain was assessed and intravenous titrated morphine was given. The primary end-point was the cumulative dose of morphine administered in the recovery room. The secondary end-points were the pain score after tracheal extubation and one hour after, the delay for obtaining a Simplified Numerical Pain Scale (SNPS) less than 4, and the incidence of morphine side effects in the recovery room.For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A p value less than 0.05 was considered as significant. RESULTS: In recovery room, morphine consumption was lower in the propacetamol group than in the placebo group (p = 0.01). Pain scores were similar in both groups after tracheal extubation and lower in the propacetamol group (p = 0.003) one hour after tracheal extubation. The time to reach a SNPS < 4 was significantly shorter in the propacetamol group (p = 0.02). The incidence of morphine related side effects did not differ between the two groups. CONCLUSIONS: Intraoperative propacetamol administration with remifentanil based-anesthesia improved significantly early postoperative pain by sparing morphine and shortening the delay to achieve pain relief.

Unanticipated difficult airway in anesthetized patients: prospective validation of a management algorithm.

BACKGROUND: Management strategies conceived to improve patient safety in anesthesia have rarely been assessed prospectively. The authors undertook a prospective evaluation of a predefined algorithm for unanticipated difficult airway management. METHODS: After a 2-month period of training in airway management, 41 anesthesiologists were asked to follow a predefined algorithm for management in the case of an unanticipated difficult airway. Two different scenarios were distinguished: "cannot intubate" and "cannot ventilate." The gum elastic bougie and the Intubating Laryngeal Mask Airway (ILMA) were proposed as the first and second steps in the case of impossible laryngoscope-assisted tracheal intubation, respectively. In the case of impossible ventilation or difficult ventilation, the IMLA was recommended, followed by percutaneous transtracheal jet ventilation. The patient's details, adherence rate to the algorithm, efficacy, and complications of airway management processes were recorded. RESULTS: Impossible ventilation never occurred during the 18-month study. One hundred cases of unexpected difficult airway were recorded (0.9%) among 11,257 intubations. Deviation from the algorithm was recorded in three cases, and two patients were wakened before any alternative intubation technique attempt. All remaining patients were successfully ventilated with either the facemask (89 of 95) or the ILMA (6 of 95). Six difficult-ventilation patients required the ILMA before completion of the first intubation step. Eighty patients were intubated with the gum elastic bougie, and 13 required a blind intubation through the ILMA. Two patients ventilated with the ILMA were never intubated. CONCLUSION: When applied in accordance with a predefined algorithm, the gum elastic bougie and the ILMA are effective to solve most problems occurring during unexpected difficult airway management.

Cardiac autonomic control during balloon carotid angioplasty and stenting.

Hemodynamic alterations during balloon carotid angioplasty (BCA) and stenting have been ascribed to the consequences of direct carotid baroreceptor stimulation during balloon inflation. BCA with stenting in patients with carotid atheromatous stenoses offers a unique opportunity for elucidating the cardiovascular autonomic response to direct transient intravascular stimulation of the baroreceptors. We analysed the consequences of BCA on the autonomic control of heart rate and on breathing components in nine patients with atheromatous stenoses involving the bifurcation and the internal carotid. A time-frequency domain method, the smoothed pseudo-Wigner-Ville transform (SPWVT), was used to evaluate the spectral parameters (i.e., the instantaneous amplitude and centre frequency (ICF) of the cardiovascular and respiratory oscillations). Those parameters and their dynamics (8 and 24 h later) were evaluated during and after the procedure. BCA stimulates baroreceptors in all patients, which markedly reduces heart rate and blood pressure. Vagal baroreflex activation altered the respiratory sinus arrhythmia in terms of amplitude and frequency (ICF HF RR shifted from 0.27 +/- 0.03 to 0.23 +/- 0.04 Hz pre-BCA vs. BCA, respectively; p < 0.01). Both the high- and low-frequency amplitudes of heart rate oscillations were altered during carotid baroreceptor stimulation, strongly supporting a contribution of the baroreflex to the generation of both oscillations of heart rate. Carotid baroreceptors stimulation increased the inspiratory time (Ti) (1.5 +/- 0.5 to 2.3 +/- 0.6 s pre-BCA vs. BCA, respectively; p < 0.01). In awake patients, BCA with stenting of atheromatous stenosis involving the bifurcation and internal carotid causes marked changes in the cardiac autonomic and respiratory control systems.

beta2-Adrenergic signaling in human heart: shift from the cyclic AMP to the arachidonic acid pathway.

We have recently established that enhancement of intracellular calcium cycling and contraction in response to beta2-adrenergic receptor (beta2-AR) stimulation exclusively relies on the activation of the cytosolic phospholipase A2 (cPLA2) and arachidonic acid production, via a pertussis toxin-sensitive G protein (possibly Gi), in embryonic chick cardiomyocytes. We aimed to investigate the relevance of the beta2-AR/Gi/cPLA2 pathway in the human myocardium. In left ventricular biopsies obtained from explanted hearts, beta2-AR stimulation exerted either an inhibition of cPLA2 that was insensitive to pertussis toxin (PTX) treatment, or an activation of cPLA2, sensitive to PTX treatment. In right atrial appendages from patients who were undergoing open heart surgery, we demonstrated that beta2-AR-induced activation of cPLA2 was favored in situations of altered beta1-AR and/or beta2-AR/adenylyl cyclase (AC) stimulations. Alterations were characterized by an increase in EC50value of norepinephrine and a decrease in the maximal AC activation in response to zinterol, respectively. Quantitative reverse transcription-polymerase chain reaction analyses highlighted a positive correlation between the expression of AC5 and AC6 mRNAs in human cardiac atria, which suggested that functional alterations in AC responses were unlikely to be related to changes in the AC5/AC6 mRNA ratio. In addition, the shift from the cyclic AMP to the arachidonic acid pathway was not supported at the transcriptional level by opposite regulation of AC and cPLA2mRNAs expression. This study gives the first evidence of the recruitment of cPLA2by beta2-ARs in the human heart and suggests that the Gi/cPLA2pathway could substitute for a deficient Gs/AC pathway in mediating beta2-AR responses.

Effect of partial liquid ventilation on bacterial clearance during Pseudomonas aeruginosa-induced lung injury in rats.

OBJECTIVE: Partial liquid ventilation (PLV) has been shown to exhibit anti-inflammatory properties during non-infectious models of acute lung injury. The aim of this experimental study was to assess the effects of PLV on bacterial clearance during Pseudomonas aeruginosa-induced pneumonia in rats. DESIGN: The rats were assigned to four groups 4 h after bacterial challenge according to the kind of mechanical ventilation [gas ventilation (GV) or PLV, 6 ml/kg perflubron plus 2 ml/kg per h] and to the level of PEEP used (3 or 8 cm of water). Physiologic measures were recorded during anesthesia (arterial blood gases, airway and blood pressures) for 4 subsequent hours until sacrifice. RESULTS: No improvement of oxygenation was demonstrated in any group. The bacterial counts were higher in PLV-PEEP 8 rats compared to GV-PEEP 8 rats: median, 1.7.10(4) cfu (25th-75th percentiles, 1.2.10(4)-1.8.10(4)) versus 1.1.10(4) (8.7.10(3)-1.3.10(4))/ml of BAL fluid and 4.0.10(6) cfu (2.0.10(6)-5.5.10(6)) versus 1.7.10(6) cfu (9.7.10(5)-3.2.10(6))/ml of lung homogenate, respectively ( P<0.05, n=8/10 surviving rats per group). PEEP 8 was associated with a significant decrease in neutrophil recruitment in BAL fluid compared to PEEP 3 in both GV and PLV groups. Additional in vitro experiments demonstrated that perflubron induced a decrease in phagocytosis of P. aeruginosa by alveolar neutrophils. CONCLUSIONS: These results demonstrate that PLV is associated with an impaired bacterial clearance during early pneumonia in rats, which could have been favored by decreased bacterial phagocytosis by neutrophils.

Discrepancies between perceptions by physicians and nursing staff of intensive care unit end-of-life decisions.

Several studies have pointed out ethical shortcomings in the decision-making process for withholding or withdrawing life-supporting treatments. We conducted a study to evaluate the perceptions of all caregivers involved in this process in the intensive care unit. A closed-ended questionnaire was completed by 3,156 nursing staff members and 521 physicians from 133 French intensive care units (participation rate, 42%). Decision-making processes were perceived as satisfactory by 73% of physicians and by only 33% of the nursing staff. More than 90% of caregivers believed that decision-making should be collaborative, but 50% of physicians and only 27% of nursing staff members believed that the nursing staff was actually involved (p < 0.001). Fear of litigation was a reason given by physicians for modifying information given to competent patients, families, and nursing staff. Perceptions by nursing staff may be a reliable indicator of the quality of medical decision-making processes and may serve as a simple and effective tool for evaluating everyday practice. Recommendations and legislation may help to build consensus and avoid conflicts among caregivers at each step of the decision-making process.

Effect of severe thrombocytopenia on patient outcome after liver transplantation.

OBJECTIVE: The objective was to identify factors associated with thrombocytopenia and to assess to what extent thrombocytopenia increases bleeding complications in liver transplant patients. DESIGN: Retrospective study. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: One hundred and sixty-one patients admitted to the intensive care unit after liver transplantation. INTERVENTION: None. MEASUREMENTS AND RESULTS: Incidence of thrombocytopenia was defined as a platelet count of <50 x 10(9)/l for at least 3 consecutive days, associated events for thrombocytopenia or bleeding were identified by a Cox proportional hazard analysis, and blood product consumption was studied. Thrombocytopenia occurred in 104 patients (65%) with a mortality rate of 18% compared with 2% in non-thrombocytopenic patients (p=0.002). Independent associated events for thrombocytopenia were need of dialysis (hazard ratio [HR], 2.30; 95% confidence interval (95% CI), 1.10-4.80) and value of preoperative platelet count (HR, 1.06; 95% CI, 1.01-1.12 by 10(4) platelet decrease). The unique associated event identified for significant bleeding was sepsis (HR, 34.80; 95% CI, 1.47-153.40). Severe thrombocytopenia led to an excess of blood product consumption (red blood cells and platelets units) during ICU stay. CONCLUSION: Thrombocytopenia of <50 x 10(9)/l for 3 days is frequent after liver transplantation and as such is not an important contributor to bleeding. However, thrombocytopenia does reflect the severity of the postoperative course.