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.

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.

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.

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.

Feasibility of closed-loop titration of propofol guided by the Bispectral Index for general anaesthesia induction: a prospective randomized study.

BACKGROUND: This study was designed to evaluate the feasibility of propofol infusion by a closed-loop system for the titration of anaesthetic induction guided by Bispectral Index. METHODS: Forty patients were prospectively and randomly allocated into two groups: the target control infusion (TCI) group, where propofol titration was performed manually guided by the Bispectral Index using a commercial pharmacokinetic model (Diprifusor device) and the closed-loop group where titration was performed using a proportional differential algorithm. For both groups, the objective was to achieve a Bispectral Index of 50. Remifentanil TCI was infused at a target of 2 ng mL-1 and was maintained constant throughout the study. Feasibility of automatic induction was evaluated with performance error and haemodynamic data. RESULTS: Bispectral Index overshoot (-9 +/- 13% vs. -16 +/- 20%, P = 0.035) and mean duration of induction (381 +/- 106 s vs. 490 +/- 131 s, P = 0.004) were lower in the closed-loop group than in the TCI group. Haemodynamic data were similar between groups with a similar use of ephedrine bolus. CONCLUSION: The system was able to allow induction clinically for all patients. Automated titration guided by Bispectral Index for propofol infusion was feasible without increase in haemodynamic adverse effects.

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.

Absence of implicit and explicit memory during propofol/remifentanil anaesthesia.

BACKGROUND AND OBJECTIVE: High doses of opioid associated with low doses of hypnotic is a popular anaesthetic technique since the use of remifentanil has become widespread. This type of anaesthesia could result in a higher incidence of implicit memory. METHODS: Ten patients were anaesthetised with a target-controlled infusion of remifentanil (target concentration of 8 ng mL(-1)) combined with a target-controlled infusion of propofol with progressive stepwise increases until loss of consciousness was reached. A tape containing 20 words was then played to the patients. Bispectral index (BIS, Aspect Medical Systems, Newton, MA, USA) was continuously monitored during the whole study period. Implicit and explicit memories were tested between 2 and 4 h after recovery. RESULTS: Loss of consciousness was obtained with a mean calculated propofol plasma concentration of 1.3 +/- 0.4 microg mL(-1). At this low hypnotic concentration no implicit or explicit memory was found in the three postoperative memory tests. Median (range) BIS value during word presentation was 93 (80-98). CONCLUSIONS: In our group of young American Society of Anesthesiologists (ASA) I/II patients, no explicit or implicit memory was found when the calculated concentration of propofol combined with a high concentration of remifentanil was maintained at the level associated with loss of consciousness with high BIS values.

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.

Effect site concentrations of remifentanil and pupil response to noxious stimulation.

BACKGROUND: Opioid drugs block reflex pupillary dilatation in response to noxious stimulation. The relationship between the target effect site concentration (Ce(T)) of remifentanil and the pupil diameter and reactivity in response to a standard noxious stimulus were evaluated. METHODS: Anaesthesia was induced with propofol TCI to obtain loss of consciousness (LOC) in 12 ASA I/II patients. Thereafter, remifentanil Ce(T) was titrated by increments of 1 up to 5 ng ml(-1). In the awake state, at LOC and at each plateau level of remifentanil Ce(T), arterial pressure, heart rate, and BIS (A2000) were recorded. Pupil size and dilatation after a 100 Hz tetanic stimulation (T100) were measured at LOC and at each plateau level of remifentanil Ce(T). RESULTS: LOC was observed at a mean propofol Ce(T) of 3.53 (SD 0.43) microg ml(-1). Arterial pressure and heart rate decreased progressively from LOC to 5 ng ml(-1) remifentanil Ce(T) without any statistical difference between each incremental dose of remifentanil. Mean BIS values decreased from 96 (2) in the awake state, to 46 (12) at LOC (P<0.05) and then remained unchanged at all remifentanil Ce(T). Pupil dilatation in response to 100 Hz tetanic stimulation decreased progressively from 1.55 (0.72) to 0.01 (0.03) mm and was more sensitive than pupil diameter measured before and after 100 Hz tetanus. An inverse correlation between pupil dilatation in response to 100 Hz tetanus and an increase in remifentanil Ce(T) from 0 to 5 ng ml(-1) was found (R(2)=0.68). CONCLUSIONS: During propofol TCI in healthy patients, the decrease in pupil response to a painful stimulus is a better measurement of the progressive increase of remifentanil Ce(T) up to 5 ng ml(-1) than haemodynamic or BIS measurements.

Absence of explicit and implicit memory in unconscious patients using a TCI of propofol.

BACKGROUND: Episodes of implicit memory have been described during propofol anaesthesia. It remains unclear whether implicit memory is caused by short periods of awareness or occurs in an unconscious subject. METHODS: Sixty patients were randomized in an experimental group (EG), a control group (CG) and a reference group (RG). Loss of consciousness (LOC) was obtained by progressive stepwise increases of propofol using a target-controlled infusion device (Diprifusor, Alaris Medical Systems, San Diego, CA). A tape containing 20 words was played to the patients in the CG before the start of anaesthesia and to the patients in the EG at a constant calculated concentration of propofol associated with LOC. The tape was not played to the patients in the RG. Three memory tests were performed postoperatively. RESULTS: Explicit and implicit memories were evidenced in the CG but not in the EG. CONCLUSION: In our group of young ASA I/II patients, in the absence of any noxious stimulus, no implicit or explicit memory was found when the calculated concentration of propofol using a Diprifusor was maintained at the level associated with LOC.

Does the platelet function analyser (PFA-100) predict blood loss after cardiopulmonary bypass?

BACKGROUND: This study was designed to determine if a new point-of-care test (PFA-100) platelet function analyser) that assesses platelet function predicts blood loss after cardiac surgery. METHODS: and results. Blood samples from 70 patients were drawn before and after cardiopulmonary bypass (CPB) for PFA-100 measurements. The system consists of a cartridge in which a membrane and an aperture are coated with either collagen/adenosine-5'-diphosphate or collagen/epinephrine. The instrument determines the time required for full occlusion of the aperture (closure time). We observed a weak correlation between pre-CPB collagen/epinephrine closure time and second-hour mediastinal blood loss (r=0.34, P=0.01). The sensitivity and positive predictive value of the PFA-100 measurements were comparable to platelet count for predicting excessive bleeding after CPB (75 and 27% vs 100 and 25%, respectively). CONCLUSIONS: The PFA-100 is a logical test for detecting patients who could have excessive bleeding after CPB. However, the PFA-100 was not able to separate patients at low risk of subsequent bleeding from those who had substantial bleeding.