Accuracy and precision of non-invasive cardiac output monitoring devices in perioperative medicine: a systematic review and meta-analysis†.

Cardiac output (CO) measurement is crucial for the guidance of therapeutic decisions in critically ill and high-risk surgical patients. Newly developed completely non-invasive CO technologies are commercially available; however, their accuracy and precision have not recently been evaluated in a meta-analysis. We conducted a systematic search using PubMed, Cochrane Library of Clinical Trials, Scopus, and Web of Science to review published data comparing CO measured by bolus thermodilution with commercially available non-invasive technologies including pulse wave transit time, non-invasive pulse contour analysis, thoracic electrical bioimpedance/bioreactance, and CO2 rebreathing. The non-invasive CO technology was considered acceptable if the pooled estimate of percentage error was <30%, as previously recommended. Using a random-effects model, sd, pooled mean bias, and mean percentage error were calculated. An I2 statistic was also used to evaluate the inter-study heterogeneity. A total of 37 studies (1543 patients) were included. Mean CO of both methods was 4.78 litres min−1. Bias was presented as the reference method minus the tested methods in 15 studies. Only six studies assessed the random error (repeatability) of the tested device. The overall random-effects pooled bias (limits of agreement) and the percentage error were −0,13 [−2.38 , 2.12] litres min−1 and 47%, respectively. Inter-study sensitivity heterogeneity was high (I2=83%, P<0.001). With a wide percentage error, completely non-invasive CO devices are not interchangeable with bolus thermodilution. Additional studies are warranted to demonstrate their role in improving the quality of care.

Preoperative frailty assessment: a review.

Elderly surgical population is growing faster than the rate of population ageing. The risk of postoperative complication is higher in this population, the type of complication and the risk indicators are different from younger patients. There is also a huge heterogeneity in the elderly population. The concept of frailty-emerges to explain these specific aspects and to risk stratify older patients. The present work intends to help the anaesthesiologist to take into account the concept of frailty at the preoperative visit. We reviewed, in the light of surgical context, the physiopathology of ageing, the definitions of frailty concept,the current existing strategies for peri-operational optimisation and the different frailty assessment tools. Our conclusions are that preoperative frailty assessment is essential in modern perioperative medicine practice and that the Edmonton Frail Scale stands out from other tools even though it cannot yet be considered as a gold standard.

Remifentanil patient-controlled analgesia effect-site target-controlled infusion compared with morphine patient-controlled analgesia for treatment of acute pain after uterine artery embolization.

BACKGROUND: Post-procedural pain control after uterine artery embolization (UAE) of urethral leiomyomata remains a major problem. METHODS: This double-blind, randomized study tested the possibility to obtain a quicker onset of analgesia by using effect-compartment controlled remifentanil patient-controlled analgesia (remifentanil TCI-PCA) than by using i.v. morphine PCA. Both systems were connected to an i.v. catheter. Active drug or matching placebo administration was activated by a single push-button. Pain was assessed using a numerical rating scale (NRS) from 0 to 10. RESULTS: NRS values were lower in the remifentanil group (with a possible difference from two to seven points on the scale) during the initial 4 h post-embolization. After the fourth hour, the NRS values were identical between the groups. No major respiratory or haemodynamic side-effect was observed. CONCLUSIONS: Remifentanil PCA-TCI with a slow and progressive adapted algorithm without any associated premedication or co-medication is feasible in young healthy women undergoing UAE.

Low-dose intravenous ketamine and clonidine for poor postoperative opioid responsiveness: a double blind randomized study.

In the immediate postoperative period, some patients present with pain that responds poorly to intravenous opioids. In a double-blind randomized study, we tested the hypothesis that administering small doses of intravenous ketamine (0.125 mg/kg) combined with clonidine (0.5 microg/kg) would enhance the speed of onset and the quality of an opioid analgesic regimen in patients who initially responded poorly to opioids. We enrolled 68 patients in the study, all physical status I to III according to the American Society of Anesthesiologists classification. If the patient's numerical rating scale (NRS) score remained > or = 5 after an initial intravenous injection of 10 mg piritramide (2-mg boluses every 5 minutes) in the post-anesthesia care unit, patients were randomized to either intravenous placebo (sodium chloride 0.9%) or active substances (ketamine 0.125 mg/kg plus clonidine 0.5 microg/kg). Fifteen minutes after administration of either placebo or active agents, patients with severe pain (NRS > 4) again received intravenous opioids until NRS < 4. The primary endpoint of the study was to reduce by 20 minutes the time necessary to achieve an NRS < 4. There was no statistically significant difference between the two groups regarding the time required for patients to achieve an NRS < 4. It was concluded that in the immediate postoperative period, the acute administration of small combined doses of intravenous ketamine (0.125 mg/kg) and clonidine (0.5 mirog/kg) does not reduce the onset of an opioid-based analgesia in patients with an initial poor response to intravenous opioids.

Ketamine has no effect on bispectral index during stable propofol-remifentanil anaesthesia.

BACKGROUND: Ketamine 0.15-1 mg kg(-1) decreases postoperative morphine consumption, but 0.5 mg kg(-1) is associated with an increase in the bispectral index (BIS) values that can lead to an overdose of hypnotic agents. The purpose of our investigation was to study the effect of ketamine 0.2 mg kg(-1) administered over a 5 min period on the BIS during stable target-controlled infusion (TCI) propofol-remifentanil general anaesthesia. METHODS: Thirty ASA I or II patients undergoing abdominal laparoscopic surgery were included in this double-blind, randomized study. Anaesthesia was induced and maintained with a TCI of propofol and remifentanil. After 5 min of steady-state anaesthesia (BIS at 40) without surgical stimulation, patients received either an infusion of ketamine 0.2 mg kg(-1) or normal saline. The test drug was infused over 5 min. Standard parameters and BIS values were recorded every minute until 15 min post-infusion. RESULTS: The baseline mean (sd) value for the BIS was 37 (6.5) for the ketamine group and 39 (8.2) for the placebo group. The highest mean BIS value during the recording period was 41.5 (8.7) for the ketamine group and 40.1 (8.9) for the placebo group. BIS values were not statistically different between the groups (P=0.62); there was no significant change over time (P=0.65) with no group-time interaction (P=0.55). CONCLUSIONS: Under stable propofol and remifentanil TCI anaesthesia, a slow bolus infusion of ketamine 0.2 mg kg(-1) administered over a 5 min period did not increase the BIS value over the next 15 min.

Effects of propofol on human microcirculation.

BACKGROUND: It is increasingly believed that acute microvascular alterations may be involved in the development of organ dysfunction in critically ill patients. Propofol significantly decreases vascular tone and venous return, which can induce arterial hypotension. However, little is known about the microcirculatory effects of propofol in healthy humans. METHODS: We conducted a prospective, open-labelled trial in 15 patients anaesthetized by propofol for transvaginal oocyte retrieval. The sublingual microcirculatory network was studied before, during, and after propofol infusion using orthogonal polarization spectral imaging. RESULTS: Mean (SD) calculated propofol effect-site concentration was 6.5 (1.8) microg ml(-1). During propofol administration, systemic haemodynamic and oxygenation variables were unchanged, but total microvascular density decreased by 9.1% (P<0.05). The venular density remained unchanged, but the density of perfused capillaries was significantly reduced by 16.7% (P<0.05). Microcirculatory alterations resolved 3 h after discontinuation of the propofol infusion. CONCLUSIONS: Propofol infusion for anaesthesia in man reduces capillary blood flow.

Haemodynamics during remifentanil induction by high plasma or effect-site target controlled infusion.

BACKGROUND: During total intravenous anaesthesia, the target controlled infusion concentration of remifentanil can be achieved either in limiting maximum plasma concentration (Cp) to the effect site target concentration which corresponds to a plasma TCI technique (pTCI) or as fast as possible to achieve the effect-site target without limiting Cp (eTCI). The aim of this study was to compare the haemodynamic effects of remifentanil pTCI and eTCI during induction of anaesthesia in ASA III patients undergoing cardiac surgery. METHODS: 28 ASA III patients, scheduled for cardiac surgery, were randomized in two groups: Group pTCI received remifentanil to achieve an effect-site target of 15 ng ml(-1) by limiting Cp to 15 ng ml(-1) and group eTCI received remifentanil to achieve an effect-site target of 15 ng ml(-1) without limiting remifentanil Cp. Before induction, all patients received 30 microg kg(-1) of midazolam intravenously and 2 ml kg(-1) of a gelatin solution. Heart rate, invasive arterial pressure and bispectral index were continuously measured. Differences from baseline values were compared between the two groups using a Mann-Whitney U test. Baseline population characteristics were compared using an analysis of variance. RESULTS: There were no significant differences in haemodynamic parameters between the two groups. In the group pTCI final effect-site concentration was reached in 7.3 +/- 1.4 minutes and in the group eTCI in 2.2 +/- 0.2 minutes (p < 0.05). CONCLUSION: In ASA III patients scheduled for elective cardiac surgery, remifentanil eTCI can be preferred to remifentanil pTCI for induction because of its shorter onset with the same haemodynamic stability.

The effect of analgesic state on implicit learning during propofol anesthesia in volunteers.

Noxious stimulation may enhance implicit learning during general anesthesia. It is unknown, however, whether analgesic state can influence this memory processing. Twenty healthy adult volunteers were enrolled our prospective, double-blinded, controlled experiments. Anesthesia was induced with a propofol target controlled infusion (TCI), titrated in step-wise increments to loss of consciousness. In phase A, a 10-word list was played to the subjects while a noxious stimulus was applied (hand immersion in cold water at 2-4 degrees C). In phase B, a remifentanil TCI infusion was added to the steady-state propofol TCI anesthesia, and titrated to loss of hand movement on cold water immersion. A second 10-word list was then played while maintaining the hand in cold water. Memory testing, 2 hours post-recovery revealed no evidence of explicit memory in any subject during either phase of the study. During phase A, the word stem completion test revealed implicit learning for played words. In contrast, no implicit memory was detected during phase B. This study indicates that analgesia with remifentanil TCI (titrated to loss of movement on noxious stimulation), prevented implicit memory processing during stable propofol anesthesia in healthy adult volunteers.

Preliminary results of prolonged target controlled infusion of sufentanil adjusted to an effort pain score after cardiac surgery.

Repeated boluses of i.v. morphine are often used for analgesia after cardiac surgery, but this procedure frequently provides inadequate pain relief. Target controlled infusion (TCI) of opioid drugs has been proposed as an alternative. The objective of this study was to evaluate the effects of prolonged sufentanil TCI adjusted to an effort pain score on the postoperative course after cardiac surgery. Twenty-six patients scheduled for cardiac surgery were anaesthetised using TCI of propofol and sufentanil, followed by early extubation. In the postoperative period, patients were randomly allocated to receive either boluses of i.v. morphine (Bolus group), adapted to a pain score at rest, or sufentanil TCI with a low target concentration (0.08-0.1 ng/ml), adapted to a pain score during deep inspiration (TCI group). Postoperative pain was assessed using a Verbal Numerical Score (VNS) before and during three stimuli: extubation, lateral positioning and physiotherapy. In 15 patients, inspiratory capacity was evaluated by incentive spirometry (IS) on postoperative day 1. Three patients in each group were withdrawn because of delayed extubation. Clinical characteristics, mean time to extubation and PaCO2 were similar in both groups. Analgesia was adequate at rest in both groups as indicated by low pain scores. Pain intensity increased significantly during the three stimuli (p < 0.01). VNS were lower in the TCI than in the Bolus group (3.8 +/- 0.5 versus 4.8 +/- 0.5, p = 0.03). Nine of 10 patients in the TCI group but only 4 of 10 patients in the bolus group gave a VNS below 5 during the stimuli. IS performance was better preserved in the TCI than in the Bolus group (53 +/- 5% versus 35 +/- 5% of preoperative values, p < 0.05). These observations indicate that after cardiac surgery, postoperative pain management with prolonged TCI of sufentanil adapted to a pain score during deep inspiration can achieve better analgesia during routine bedside procedures and higher pulmonary volumes than on-demand boluses of morphine.

Combination of minimally invasive coronary bypass and percutaneous transluminal coronary angioplasty in the treatment of double-vessel coronary disease: Two-year follow-up of a new hybrid procedure compared with "on-pump" double bypass grafting.

OBJECTIVE: Percutaneous transluminal coronary angioplasty (PTCA) or surgery can be chosen as first-line therapies in multiple-vessel coronary disease. A mammary-to-left anterior descending (LAD) graft is the most important statistical determinant of a favorable outcome after coronary artery bypass grafting (CABG) and can be performed with lower morbidity off pump through a minithoracotomy. PTCA and stenting of the "non-LAD" vessels compete with CABG in terms of patency rates. Our purpose was to compare a combination of minimally invasive direct coronary artery bypass (MIDCAB) and PTCA with double CABG as a treatment for double-vessel coronary artery disease involving the proximal LAD. METHODS: Two matched groups of 20 patients with double-vessel coronary disease undergoing either sequential MIDCAB and PTCA (group 1) or double CABG on cardiopulmonary bypass (group 2) were compared. Angiographic control, complications, hospital costs, quality of life, and 2-year follow-up of ischemia are reported. RESULTS: All bypasses were patent at early control. Three adverse events were noted in group 1 and 17 in group 2. The hybrid-procedure group exhibited a shorter intensive care unit stay, fewer blood products transfused, less pain, better early quality of life, faster return to work, and similar cost. Three patients required a second PTCA in group 1, one of which for restenosis. At 2 years all the patients are asymptomatic with no residual ischemia. CONCLUSIONS: We conclude from this pilot study that the hybrid procedure is feasible and appears to be a safe therapy for double-vessel coronary artery disease and that it appears to generate less perioperative morbidity than classic double CABG does. Therefore we believe that there is room to undertake prospective randomized studies on a larger-scale basis.

Myocardium is a major source of proinflammatory cytokines in patients undergoing cardiopulmonary bypass.

Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-6, and interleukin-8, and anti unflammatory cytokines, such as interleukin-10, may play an important role in patient responses to cardiopulmonary bypass. We sought to define whether the myocardium and the lungs serve as important sources of these cytokines under conditions of cardiopulmonary bypass. Ten patients (age 64 +/- 3 years, mean +/- standard error of the mean) undergoing elective coronary artery bypass grafting were monitored with an arterial catheter, a coronary sinus catheter, and pulmonary artery catheter. Plasma levels of tumor necrosis factor-alpha, interleukin-6, interleukin-8, and interleukin-10 were measured simultaneously in peripheral arterial blood, coronary sinus blood, and mixed venous blood before heparin administration, 1 minute before aortic crossclamping, 5 minutes after aortic declamping, and at 0.5, 1, 1.5 and 2 hours after aortic declamping. The durations of cardiopulmonary bypass and aortic crossclamping were 114 +/- 9 and 64 +/- 5 minutes, respectively. Levels of tumor necrosis factor-alpha and interleukin-6 were significantly higher in coronary sinus blood than in arterial blood after aortic declamping. Tumor necrosis factor-alpha and interleukin-6 levels were also higher in mixed venous blood than in arterial blood within 1 hour after declamping. There were no significant differences among the three sampling sites with respect to interleukin-8 and interleukin-10 levels. In one patient who had postoperative myocardial infarction, however, interleukin-8 levels were three times as high as in coronary sinus blood than in arterial blood. These data indicate that the myocardium is a major source of tumor necrosis factor-alpha and interleukin-6 in patients undergoing cardiopulmonary bypass. The lungs may consume rather than release proinflammatory cytokines in the early phase of reperfusion. The source under these conditions of the antünflammatory cytokine interleukin-10 remains to be determined.

Corticosteroids increase blood interleukin-10 levels during cardiopulmonary bypass in men.

BACKGROUND: Interleukin (IL)-10 is a potent antiinflammatory cytokine inhibiting the release of tumor necrosis factor--alpha (TNF-alpha) and IL-8 by activated macrophages and polymorphonuclear leukocytes. Cardiopulmonary bypass (CPB) represents a unique situation where an inflammatory reaction is predictably induced. The present study examined the influence of CPB on the release of TNF-alpha, IL-1 beta, IL-8, and IL-10 and also defined the effects of pretreatment with corticosteroids on the release of these cytokines. METHODS: The study included 22 patients undergoing coronary artery bypass graft operations, including eight control patients and seven patients who received dexamethasone, and seven patients who received methylprednisolone 4 hours before the operation. Cytokines were measured with the enzyme-linked immunosorbent assay technique before treatment, before anesthesia induction, immediately before heparin administration, before aorta declamping, 10 minutes and 90 minutes after aorta declamping, and 4 hours after the end of CPB. RESULTS: In the control patients the TNF-alpha levels and especially the IL-8 levels increased during CPB and reached their maximal levels 4 hours after CPB. IL-10 levels rose moderately and transiently, reaching peak values 90 minutes after aorta declamping. Notably, administration of corticosteroids prevented IL-8 release but increased IL-10 levels, which were tenfold higher than in the control group 90 minutes after aorta declamping (dexamethasone, 271 +/- 128 pg/ml; methylprednisolone, 312 +/- 213 pg/ml; control, 17 +/- 12 pg/ml, p < 0.05). IL-1 beta was not detected in any group of patients. CONCLUSIONS: The present data indicate that IL-10 is released together with proinflammatory cytokines during and after CPB and that pretreatment with corticosteroids markedly enhances this release. The release of IL-10 may play an important role in the antiinflammatory effects of corticosteroids.

Predictive accuracy of midazolam in adult patients scheduled for coronary surgery.

STUDY OBJECTIVE: To evaluate the predictive accuracy of midazolam during cardiac anesthesia so as to orient the selection of the most appropriate pharmacokinetic model for use in a computer-assisted continuous-infusion system. DESIGN: Retrospective analysis. SETTING: Operating room at a university hospital. PATIENTS: 66 consecutive middle-aged and elderly coronary patients scheduled for coronary artery bypass graft (CABG) surgery. INTERVENTIONS: Patients were anesthetized using a variable-rate infusion of alfentanil combined with midazolam in an attempt to achieve and maintain target concentrations of 100 ng/ml or 500 ng/ml. MEASUREMENTS AND MAIN RESULTS: A total of 323 arterial blood samples were taken, and serum midazolam concentrations were measured by high-performance liquid chromatography. Predicted midazolam concentrations were calculated using 3 selected data sets. Their bias, inaccuracy, and dispersion were assessed by determining the median performance error, the median absolute performance error (MDAPE), and the 10th and 90th percentiles. Two of the selected data sets of midazolam, with a clearance lower than 5 ml/kg/min, were very accurate (MDAPE less than 20%) in predicting low or high prebypass concentrations of midazolam in adult patients with good left ventricular function. CONCLUSIONS: Two of the 3 pharmacokinetic data sets of midazolam studied may be selected when using a computer-assisted infusion system in adult coronary patients.

A study of the action of oral cimetidine or placebo on the pH and the volume of gastric contents when administered the evening or the morning before general anesthesia. A double blind study.

A double blind experiment studied the effect on the pH and on the volume of gastric fluid after the administration of either cimetidine or a placebo as premedication before scheduled operations. The patients were divided into 4 groups. Group A received 400 mg of cimetidine the night before the operation and the placebo in the morning. Group B received 400 mg of cimetidine the night before and 200 mg in the morning. Group C received the placebo in the evening and in the morning and group D received the placebo in the evening and 200 mg of cimetidine in the morning. Compared to the placebo group C, the action of cimetidine on the pH was only significant in the 2 groups (B, D) which received a morning dose (p less than 0.01), but cumulative evening and morning administration of cimetidine (group B) was the only method which statistically diminished the mean volume of gastric fluid (p less than 0.05). The administration of repeated doses of cimetidine increased the pH and decreased the volume of gastric fluid and would thus seem to be a good method to prevent inhalation pneumonia during anesthesia.

Continuous infusion of midazolam or bolus of diazepam for postoperative sedation in cardiac surgical patients.

Sedation and recovery were studied in 14 patients requiring overnight ventilation in the ICU after aortocoronary bypass surgery performed under high-dose fentanyl anesthesia (120 micrograms/kg). Patients received either IV bolus of diazepam (group D) or a combination of IV bolus with a continuous infusion of midazolam (group M). In the 2 groups, an on-demand mode of administration was used to provide optimal sedation. In the ICU, dosages of plasma catecholamines and serum benzodiazepines were performed. After cessation of benzodiazepine administration at midnight, the rapidity of recovery and time of extubation were recorded. Results showed that in the 2 groups, the association of a high-dose fentanyl anesthesia with a profound postoperative sedation maintained the epinephrine and norepinephrine concentrations at low levels during the whole postoperative period. After benzodiazepine discontinuation, recovery and extubation were faster in group M, which correlated with the significant decrease (p less than 0.05) in blood concentration of midazolam observed the first postoperative day whereas at the same time the blood concentration of diazepam did not fall significantly.

[Atracurium in the elderly subject]. / L'atracurium chez le sujet âgé.

The effects of age on the pharmacodynamics of atracurium have been studied in twenty-four consenting adult patients undergoing elective surgery. They were divided in three groups according to their age (mean +/- SEM): group 1 (n = 8; 26 +/- 3 yr), group 2 (n = 8; 53 +/- 2 yr) and group 3 (n = 8; 76 +/- 2 yr). Anaesthesia was induced with methohexitone (1 mg . kg-1) and fentanyl (5 micrograms . kg-1), and maintained with 66% N2O plus fentanyl on demand. Ventilation was controlled and adjusted to produce normocapnia. The isometric contraction of the adductor pollicis muscle in response to supramaximal cubital nerve stimulation delivered at 0.1 Hz was measured with a force displacement transducer. A loading dose of atracurium (0.3 mg . kg-1) was given before tracheal intubation. Thereafter, twitch height (TH) was maintained at 10% of its baseline reading by adjusting the flow of a Harvard syringe containing 0.5 mg . ml-1 of atracurium in saline. The amount of atracurium required to maintain a stable twitch height, calculated for a 60 min period, was 14.7 +/- 1 mg . m-2 . h-1 for group 1, 13.6 +/- 1.5 mg . m-2 . BSA-1 for group 2 and 15 +/- 2.1 mg . m-2 . BSA-1 for group 3. At the end of the infusion period, the TH25-75 recovery rates were not statistically different in the three groups: 15.4 +/- 1.9 min for group 1, 14.8 +/- 1.1 min for group 2 and 14.5 +/- 1.6 min for group 3.(ABSTRACT TRUNCATED AT 250 WORDS)