The effect of peri-operative dexmedetomidine on the incidence of postoperative delirium in cardiac and non-cardiac surgical patients: a randomised, double-blind placebo-controlled trial.

Delirium occurs commonly following major non-cardiac and cardiac surgery and is associated with: postoperative mortality; postoperative neurocognitive dysfunction; increased length of hospital stay; and major postoperative complications and morbidity. The aim of this study was to investigate the effect of peri-operative administration of dexmedetomidine on the incidence of postoperative delirium in non-cardiac and cardiac surgical patients. In this randomised, double-blind placebo-controlled trial we included 63 patients aged ≥ 60 years undergoing major open abdominal surgery or coronary artery bypass graft surgery with cardiopulmonary bypass. The primary outcome was the incidence of postoperative delirium, as screened for with the Confusion Assessment Method. Delirium assessment was performed twice daily until postoperative day 5, at the time of discharge from hospital or until postoperative day 14. We found that dexmedetomidine was associated with a reduced incidence of postoperative delirium within the first 5 postoperative days, 43.8% vs. 17.9%, p = 0.038. Severity of delirium, screened with the Intensive Care Delirium Screening Checklist, was comparable in both groups, with a mean maximum score of 1.54 vs. 1.68, p = 0.767. No patients in the dexmedetomidine group died while five (15.6%) patients in the placebo group died, p = 0.029. For patients aged ≥ 60 years undergoing major cardiac or non-cardiac surgery, we conclude that the peri-operative administration of dexmedetomidine is associated with a lower incidence of postoperative delirium.

Impact of brief prewarming on anesthesia-related core-temperature drop, hemodynamics, microperfusion and postoperative ventilation in cytoreductive surgery of ovarian cancer: a randomized trial.

BACKGROUND: General (GA)- and epidural-anesthesia may cause a drop in body-core-temperature (BCTdrop), and hypothermia, which may alter tissue oxygenation (StO2) and microperfusion after cytoreductive surgery for ovarian cancer. Cell metabolism of subcutaneous fat- or skeletal muscle cells, measured in microdialysis, may be affected. We hypothesized that forced-air prewarming during epidural catheter placement and induction of GA maintains normothermia and improves microperfusion. METHODS: After ethics approval 47 women scheduled for cytoreductive surgery were prospectively enrolled. Women in the study group were treated with a prewarming of 43 °C during epidural catheter placement. BCT (Spot on®, 3 M) was measured before (T1), after induction of GA (T2) at 15 min (T3) after start of surgery, and until 2 h after ICU admission (TICU2h). Primary endpoint was BCTdrop between T1 and T2. Microperfusion-, hemodynamic- and clinical outcomes were defined as secondary outcomes. Statistical analysis used the Mann-Whitney-U- and non-parametric-longitudinal tests. RESULTS: BCTdrop was 0.35 °C with prewarming and 0.9 °C without prewarming (p < 0.005) and BCT remained higher over the observation period (ΔT4 = 0.9 °C up to ΔT7 = 0.95 °C, p < 0.001). No significant differences in hemodynamic parameters, transfusion, arterial lactate and dCO2 were measured. In microdialysis the ethanol ratio was temporarily, but not significantly, reduced after prewarming. Lactate, glucose and glycerol after PW tended to be more constant over the entire period. Postoperatively, six women without prewarming, but none after prewarming were mechanical ventilated (p < 0.001). CONCLUSION: Prewarming at 43 °C reduces the BCTdrop and maintains normothermia without impeding the perioperative routine patient flow. Microdialysis indicate better preserved parameters of microperfusion. TRIAL REGISTRATION: ClinicalTrials.gov ; ID: NCT02364219 ; Date of registration: 18-febr-2015.

Risk factors for 30-day complications after cancer surgery in geriatric patients: a secondary analysis.

BACKGROUND: The aim was to analyse the association between severity of complications up to 30 days after surgery and pre-operative nutritional and physical performance parameters. METHODS: The participants were a subsample of the previously published PERATECS study (ClinicalTrials.gov: NCT01278537) and included 517 onco-geriatric patients aged ≥ 65 years, undergoing thoracoabdominal, gynaecological, or urological surgery. Post-operative complications were classified according to the Clavien Classification System (CCS). Independent risk factors related to the severity of complications, defined as major complications (CCS IIIa-V) and graded complications (CCS grade 0-V), were analysed using logistic and ordinal regression, respectively. RESULTS: In total, 132 patients suffered major post-operative complications. The development of major post-operative complications was independently associated with body mass index (BMI) < 20 kg/m2 , hypoalbuminaemia (< 30 g/l), longer duration of surgery, and specific tumour sites (upper gastrointestinal, gynaecological, colorectal) (all P < 0.05). Higher-grade complications were predicted by Timed Up and Go (TUG) > 20 s, hypoalbuminaemia (< 30 g/l), higher American Society of Anesthesiologists (ASA) status III-IV, longer duration of surgery (> 165 min), and specific tumour sites (upper gastrointestinal, gynaecological) (all P < 0.05). Mini Nutritional Assessment (MNA) scores and weight loss were not independent risk factors for the severity of complications. CONCLUSIONS: Nutritional and physical performance risk factors that predicted the severity of complications differed between major and higher-grade post-operative complications, but hypoalbuminaemia independently predicted both. The results support the need for pre-operative risk screening. Due to the explorative nature of the study, further research is required in larger cohorts to corroborate these findings.

No convincing association between post-operative delirium and post-operative cognitive dysfunction: a secondary analysis.

BACKGROUND: Post-operative delirium and post-operative cognitive dysfunction (POCD) are both common but it has not been clarified how closely they are associated. We aimed to assess the possible relationship in a secondary analysis of data from the 'Surgery Depth of anaesthesia and Cognitive outcome'- study. METHODS: We included patients aged ≥ 60 years undergoing non-cardiac surgery planned for longer than 60 min. Delirium was assessed according to the Diagnostic and Statistical Manual of Mental Disorders IV criteria in the post-anaesthesia care unit (PACU) as well as within the first week after surgery. Cognitive function was assessed with a neuropsychological test battery. Multivariable analysis of POCD was performed with consideration of predisposing and precipitating factors. RESULTS: Of 1277 randomized patients, 850 (66.6%) had complete data. Delirium was found in 270 patients (32.9% of 850). We detected POCD in 162 (20.9% of 776) at 1 week and in 52 (9.4% of 553) at 3 months. In multivariable analysis (n = 808), delirium had no overall effect on POCD (P = 0.30). Patients with no delirium in PACU but with postoperative delirium within 7 days had an increased risk of POCD at 3 months (OR = 2.56 (95%-confidence interval: 1.07-6.16), P = 0.035). No significant association was found for the other subgroups. CONCLUSIONS: There is no clear evidence that postoperative delirium is independently associated with POCD up to 3 months.

Obesity in regional anesthesia--a risk factor for peripheral catheter-related infections.

BACKGROUND: Obesity is believed to increase the risk of surgical site infections and possibly increase the risk of catheter-related infections in regional anesthesia. We, therefore, analyzed the influence of obesity on catheter-related infections defined within a national registry for regional anesthesia. METHODS: The German Network for Regional Anesthesia database with 25 participating clinical centers was analyzed between 2007 and 2012. Exactly, 28,249 cases (13,239 peripheral nerve and 15,010 neuraxial blocks) of patients ≥ 14 years were grouped in I: underweight (BMI 13.2-18.49 kg/m(2) , n = 597), II: normal weight (BMI 18.5-24.9 kg/m(2) , n = 9272), III: overweight (BMI 25.0-29.9 kg/m(2) , n = 10,632), and IV: obese (BMI 30.0-70.3 kg/m(2) , n = 7,744). The analysis focused on peripheral and neuraxial catheter-related infections. Differences between the groups were tested with non-parametric ANOVA and chi-square (P < 0.05). Binary logistic regression was used to compare obese, overweight, or underweight patients with normal weight patients. Odds ratios (OR and 95% confidence interval) were calculated and adjusted for potential confounders. RESULTS: Confounders with significant influence on the risk for catheter-related infections were gender, age, ASA score, diabetes, preoperative infection, multiple skin puncture, and prolonged catheter use. The incidence (normal weight: 2.1%, obese: 3.6%; P < 0.001) and the risk of peripheral catheter-related infection was increased in obese compared to normal weight patients [adjusted OR: 1.69 (1.25-2.28); P < 0.001]. In neuraxial sites, the incidence of catheter-related infections differed significantly between normal weight and obese patients (normal weight: 3.2%, obese: 2.3%; P = 0.01), whereas the risk was comparable [adjusted OR: 0.95 (0.71-1.28); P = 0.92]. CONCLUSION: This retrospective cohort study suggests that obesity is an independent risk factor for peripheral, but not neuraxial, catheter-related infections.

Preoperative depression and hospital length of stay in surgical patients.

BACKGROUND: The association of depression and hospital length of stay (LOS) has rarely been examined in surgical patients outside of cardiovascular surgery. This study investigates whether clinically significant preoperative depression shows an independent association with LOS in patients from various surgical fields after adjusting for age, gender and important somatic factors. METHODS: A total of 2624 surgical patients were included in this prospective observational study. Data were collected before the preoperative anesthesiological examination within a computer-assisted psychosocial self-assessment including screening for depression (Center for Epidemiologic Studies Depression Scale, CES-D). Data on peri- and postoperative somatic parameters were obtained from the electronic patient management system of the hospital six months after the preoperative assessment. RESULTS: LOS of patients with clinically significant depression (N.=296; median: 5 days, interquartile range: 3-8 days) was longer than LOS of patients without depression (N.=2328; median: 4 days, interquartile range: 2-6 days) (P<0.001). A multivariate logistic regression model with the binary dependent variable 'above versus below or equal to the median LOS' revealed that the significant association between depression and LOS persisted (OR: 1.822 [95% CI 1.360-2.441], P<0.001) when simultaneously including the covariates age, gender, ASA classification, Charlson Comorbidity Index, surgical field and POSSUM operative severity rating. CONCLUSION: Data suggest that the association of depression and LOS is independent of the impact of age, gender, surgical field, preoperative physical health, severity of medical comorbidity and extent of surgical procedure. Integration of depression therapy into routine care of surgical patients might be an option to improve outcomes.

Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction.

BACKGROUND: Postoperative delirium in elderly patients is a frequent complication and associated with poor outcome. The aim of this parallel group study was to determine whether monitoring depth of anaesthesia influences the incidence of postoperative delirium. METHODS: Patients who were planned for surgery in general anaesthesia expected to last at least 60 min and who were older than 60 yr were included between March 2009 and May 2010. A total of 1277 patients of a consecutive sample were randomized (n=638 open, n=639 blinded) and the data of 1155 patients were analysed (n=575 open, n=580 blinded). In one group, the anaesthesiologists were allowed to use the bispectral index (BIS) data to guide anaesthesia, while in the other group, BIS monitoring was blinded. Cognitive function was evaluated at baseline, 1 week, and 3 months after operation. RESULTS: Delirium incidence was lower in patients guided with BIS. Postoperative delirium was detected in 95 patients (16.7%) in the intervention group compared with 124 patients (21.4%) in the control group (P=0.036). In a multivariate analysis, the percentage of episodes of deep anaesthesia (BIS values <20) were independently predictive for postoperative delirium (P=0.006; odds ratio 1.027). BIS monitoring did not alter the incidence of postoperative cognitive dysfunction (7th day P=0.062; 90th day P=0.372). CONCLUSIONS: Intraoperative neuromonitoring is associated with a lower incidence of delirium, possibly by reducing extreme low BIS values. Therefore, in high-risk surgical patients, this may give the anaesthesiologist a possibility to influence one precipitating factor in the complex genesis of delirium. Clinical trial registration ISRCTN Register: 36437985. http://www.controlled-trials.com/ISRCTN36437985/.

Incidence and risk factors for cognitive dysfunction in patients with severe systemic disease.

OBJECTIVE: To determine the relevance of surgery and other causative factors to the incidence of postoperative cognitive dysfunction (POCD) in patients with severe systemic disease. METHODS: This observational study included 107 noncardiac surgical patients and 26 nonsurgical control subjects, all of whom had an American Society of Anesthesiologists physical classification status of 3. Cognitive assessment was performed preoperatively and 7 days postoperatively, or with a 7-day interval for the control group. POCD was calculated as a combined Z-score. Mini Mental State Examination (MMSE) was used to exclude patients with pre-existing cognitive deficit (MMSE score ≤ 23). Surgical and other factors including duration of surgery/anaesthesia and length of stay in the intensive care unit (ICU) were recorded. RESULTS: After 7 days, POCD was found in 40/107 (37.4%) surgical patients compared with 4/26 (15.4%) nonsurgical controls. Preoperative MMSE score, duration of surgery/anaesthesia, and length of stay in the ICU and hospital were associated with POCD. Logistic regression analysis revealed that preoperative MMSE score was an independent predictor of POCD. CONCLUSION: Lower baseline MMSE score was the only independent predictor for POCD in patients with severe systemic disease.

[Delirium in the intensive care unit : Overview for nurses and physicians]. / Das Delir auf Intensivstationen : Ein Überblick für Pflegekräfte und Ärzte.

Delirium is a severe but frequent organ dysfunction in intensive care units (ICU) affecting nearly 80% of mechanically ventilated patients and up to 50% of non-ventilated patients. Although guidelines for diagnosis and treatment of delirium exist it often remains underdiagnosed due to the lack of implementation of these guidelines. Therefore, the chance of a positive outcome for patients can be significantly reduced. Delirium results in longer mechanical ventilation, extended hospital stay, more nosocomial infections and an increased mortality. Measures which improve the frequency of diagnosis and increase the quality of treatment will only be successful if physicians, nursing staff and other medical staff on ICUs realize strategies together and raise their awareness on delirium.

Do hospital treatments represent a 'teachable moment' for quitting smoking? A study from a stage-theoretical perspective.

Hospital treatments are assumed to be a 'teachable moment'. This phenomenon, however, is only poorly conceptualised and untested. A stage-theoretical perspective implies that a cueing event such as hospital treatments is a teachable moment if a stage progression, change of cognitions, or both occur. This concept is examined in a cross-sectional study by comparing smokers in two treatment settings, an emergency department (ED) and inpatient treatment after elective surgery, with smokers in a control setting. Setting differences were hypothesised in stage distribution, and levels of and stage differences in social-cognitive factors under control for possible confounders. Stage, social-cognitive factors and possible confounders were assessed in 185 ED smokers, 193 inpatient smokers and 290 control smokers. Compared to control smokers, ED and inpatient smokers were in higher stages; they perceived fewer risks and cons; inpatient smokers reported more concrete plans. Stage differences in self-efficacy among ED and inpatient smokers differed from those among control smokers, but the former corresponded more strongly to the theoretical stage assumptions. The results suggest that hospital treatments lead to a stage progression and change of corresponding cognitions, and thus represent a 'teachable moment'. Stage-matched interventions should be provided but consider differences in cognitions to be effective.

Documented intraoperative hypotension according to the three most common definitions does not match the application of antihypotensive medication.

This observational study investigated which of the three most common definitions of intraoperative hypotension (IOH), reported in a published systematic literature review, were associated best with anaesthetists' administration of antihypo tensive medication (AHM). IOH and AHM use in anaesthetic procedures in a mixed surgical population (n = 2350) were also reviewed. The definitions were: arterial systolic blood pressure (SBP) < 100 mmHg or a fall in SBP of > 30% of the preoperative SBP baseline; arterial SBP < 80 mmHg; a fall in SBP of > 20% of the preoperative SBP. Accuracy of predicting AHM using these three definitions was 67%, 54% and 65%, respectively. Prediction by a new fourth definition, using an optimal threshold of minimal SBP falling to < 92 mmHg or by > 24% of preoperative baseline, was 68% accurate. In multivariate logistic analysis, age, volatile versus intravenous anaesthetics, medical history of arterial hypertension and all four definitions of IOH were associated with intraoperative AHM, however IOH was not associated with postoperative in-patient stay. The three original definitions correlated poorly with the anaesthetist's judgement about applying AHM. Anaesthetists make complex decisions regarding the relevance of IOH, considering various perioperative factors in addition to SBP. Age, physical status and duration and type of surgery showed better correlations with postoperative in-patient stay than IOH.

Adherence to guideline-based standard operating procedures in pre-hospital emergency patients with chronic obstructive pulmonary disease.

This study investigated improvements in pre-hospital care for patients with acute exacerbated chronic obstructive pulmonary disease (aeCOPD) achieved by using a standard operating procedure (SOP). An SOP for pre-hospital treatment of patients with aeCOPD was designed based on valid national guidelines. A total of 1000 Emergency Medical Service patient care reports were analysed prospectively: 500 before and 500 after introduction of the SOP. Overall guideline adherence was 34.6% before and 53.8% after introduction of the SOP; this increase was not statistically significant. After SOP introduction, the administration of ß(2) mimetics by inhalative, intravenous and subcutaneous routes increased significantly. The level of knowledge of the national guidelines was rated at 67% by emergency physicians during self-assessment, but was only 33% when physicians were asked specific questions during interview. Introducing the SOP for patients with aeCOPD did not significantly improve adherence to valid national guidelines, but did help to improve specific elements of therapy.

Strategies for diagnosis and treatment of iatrogenic tracheal ruptures.

BACKGROUND: Management of tracheal ruptures in critically ill patients is challenging. Conservative treatment has been described, but in mechanically ventilated patients with distal tracheal ruptures surgical repair might be inevitable. Strategies for diagnosis and treatment of tracheal ruptures and handling of mechanical ventilation remain to be clarified. Our aim was to comprise a structured diagnostic and treatment protocol for patients suspicious of tracheal injury, including detailed principles of mechanical ventilation and specific indications for conservative or surgical treatment. METHODS: Patients with tracheal ruptures were compared in accordance to the need of mechanical ventilation and to indication for surgical repair. In patients suffering from tracheal ruptures affecting the whole tracheal wall and with protrusion of mediastinal structures into the lumen surgery was indicated. We compared ventilatory, hemodynamic and clinical parameters between the different patient groups. We report our structured approach in diagnostics and treatment of tracheal ruptures and place special emphasis on respiratory management. RESULTS: Seventeen patients with tracheal rupture were identified. In 8 patients surgical repair was performed 1.8±1.5 days after diagnosis. Previous to surgery, ventilation parameters improved significantly: plateau pressure decreased, percentage of assisted spontaneous breathing increased and compliance improved. Conservative treatment was successful in long-term ventilated patients (13.7±8 days) even when suffering from distal lesions. CONCLUSION: Invasiveness of mechanical ventilation and obstruction of tracheal lumen might indicate conservative or surgical treatment strategies in long-term ventilated patients suffering from iatrogenic tracheal rupture. Indications for surgical repair remain to be further clarified.

Remifentanil reduces the incidence of post-operative delirium.

A secondary exploratory analysis of data from an observational study was used to study the influence of the opioid used for intraoperative anaesthesia on the incidence of post-operative delirium. Patients who had been admitted to the recovery room following elective general anaesthesia were divided into those who had received fentanyl or remifentanil. For unbiased patient analysis, matched pairs were built with respect to gender, age, physical status, anaesthetic type and surgery duration. In 752 patients, the overall incidence of delirium was 9.9% in the recovery room and 3.8% on the first post-operative day. Compared with the remifentanil group, the fentanyl group had a significantly higher incidence of delirium in the recovery room (12.2% versus 7.7%) and on the first post-operative day (5.8% versus 1.9%). Delirium in the recovery room and on the first post-operative day were both associated with a significantly prolonged post-operative hospital stay. The choice of intraoperative opioid influences the incidence of post-operative delirium. Remifentanil was associated with a lower incidence of post-operative delirium in the early post-operative period.

Documentation of post-operative nausea and vomiting in routine clinical practice.

This study investigated the quality of documentation of post-operative nausea and vomiting (PONV) by comparing incidences collected by a research team with those reported routinely by nursing personnel. A total of 560 patients passing through an interdisciplinary recovery room were included in the study. The overall recorded incidence of PONV over 24 h was 30.7%, which was in agreement with the predicted value of 32% calculated using incidences from published randomized controlled trials. Out of the total number of 86 cases of PONV in the recovery room only 36 (42%) were detected by nursing staff. Similarly, out of the total number of 129 cases of PONV on the ward over 24 h, only 37 (29%) were recognized by nursing staff during routine care. In conclusion, PONV in routine clinical care is likely to be under-reported. To use PONV as a valid quality measure, patients need to be actively asked about nausea and vomiting at frequent intervals in a standardized fashion. A considerable proportion of patients experience PONV after discharge from the recovery room, so the assessment of PONV should cover at least 24 h post-operatively.

Risk factors for inadequate emergence after anesthesia: emergence delirium and hypoactive emergence.

AIM: Inadequate emergence after anesthesia in the adult patient may be distinguished by the patients' activity level into two subtypes: emergence delirium and hypoactive emergence. The aim of this study was to determine the incidence of inadequate emergence in its different forms, to identify causative factors and to examine the possible influence on postoperative length of stay in the recovery room and in the hospital. METHODS: In this prospective observational study, 1868 non-intubated adult patients who had been admitted to the recovery room were analyzed. Inadequate emergence was classified in its different forms according to the Richmond agitation and sedation scale (RASS) 10 minutes after admission to the recovery room. Emergence delirium was defined as a RASS score >or=+1, and hypoactive emergence was defined as a RASS score

[Adherence to treatment guidelines for postoperative nausea and vomiting. How well does knowledge transfer result in improved clinical care?]. / Einhaltung der Behandlungsrichtlinien für postoperative Ubelkeit und Erbrechen. Wie gut gelingt der Wissenstransfer hin zu einer besseren klinischen Versorgung?

BACKGROUND: In order to reduce the incidence of postoperative nausea and vomiting (PONV) a standard operating procedure (SOP) was developed in our department. This consists basically in the administration of one antiemetic intervention for moderate risk (2 risk factors), two interventions for high risk (3-4 risk factors) and no prophylaxis in patients who have no or only one risk factor. The aim of this study was to find out whether PONV prophylaxis according to our SOP was followed and led to a lower incidence of PONV. METHOD AND PATIENTS: A total of 2,729 patients were examined in a prospective observational study with post-ad hoc analysis in our department. Inclusion criteria were age over 14 years after general anesthesia and postoperative care in the recovery room. This group was examined in relation to compliance with the SOP. RESULTS: A total of 725 (26.6%), 1050 (38.5%) and 954 (35.0%) patients were grouped according to risk classification into groups with low, medium and high risks, respectively. An SOP compliant regime occurred in 668 patients (92.1%) of the low risk groups, in 373 patients (35.6%) of the moderate risk group and 177 patients (18.6%) of patients at high risk for PONV. In the high risk group 565 patients (59.2%) received at least one antiemetic medication. Patients with PONV were on average cared for 12 min longer in the recovery room (p=0.048). CONCLUSION: Patients with medium and high risk have a lower incidence of PONV than expected per risk calculation by complying with the SOP. However, the recommended risk-adapted approach was inadequately implemented. Considering this there is room for improvement. Moreover taking into account these implementation issues a general PONV prophylaxis may be beneficial.

Improving the detection of illicit substance use in preoperative anesthesiological assessment.

AIM: Illicit substance use (ISU) is a worldwide burden, and its prevalence in surgical patients has not been well investigated. Co-consumption of legal substances, such as alcohol and tobacco, complicates the perioperative management and is frequently underestimated during routine preoperative assessment. The aim of this study was to compare the anesthesiologists' detection rate of ISU during routine preoperative assessment with a computerized self-assessment questionnaire. METHODS: In total, 2,938 patients were included in this study. Prior to preoperative assessment, patients were asked to complete a computer-based questionnaire that addressed ISU, alcohol use disorder (AUDIT), nicotine use (Fagerström) and socio-economic variables (education, income, employment, partnership and size of household). Medical records were reviewed, and the anesthesiologists' detection of ISU was compared to the patients' self-reported ISU. RESULTS: Seven point five percent of patients reported ISU within the previous twelve months. ISU was highest in the age group between 18 and 30 years (26.4%; P<0.01). Patients reporting ISU were more often men than women (P<0.01), smokers (P<0.01) and tested positive for alcohol use disorder (P<0.01). Anesthesiologists detected ISU in one in 43 patients, whereas the computerized self-assessment reported it in one in 13 patients. The detection was best in the subgroup self-reporting frequent ISU (P<0.01). CONCLUSIONS: Anesthesiologists underestimate the prevalence of ISU. Computer-based self-assessment increases the detection of ISU in preoperative assessment and may decrease perioperative risk. More strategies to improve the detection of ISU as well as brief interventions for ISU are required in preoperative assessment clinics.

Profound haemodilution during normothermic cardiopulmonary bypass influences neither gastrointestinal permeability nor cytokine release in coronary artery bypass graft surgery.

BACKGROUND: Cardiopulmonary bypass (CPB) impairs intestinal barrier function and induces systemic inflammation after cardiac surgery. The objective of this study was to evaluate the effect of profound haemodilution (haematocrit 19-21%) during normothermic CPB on gastrointestinal permeability and cytokine release in comparison with a standard haemodilution (haematocrit 24-26%). METHODS: This was a prospective, controlled, randomized pilot trial of 60 patients without gastrointestinal disease undergoing normothermic CPB (35.5-36 degrees C) for coronary artery bypass graft surgery. Gastrointestinal permeability was measured by the triple-sugar technique (sucrose, lactulose, and mannitol excretion in urine) before and after CPB. Interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNFalpha) were quantified using enzyme-linked immunosorbent assays. RESULTS: Data from 59 patients (19-21% haematocrit, n=28; 24-26% haematocrit, n=31) were analysed. Data on gastrointestinal permeability were available for 47 patients (19-21% haematocrit, n=23; 24-26% haematocrit, n=24), blood samples for cytokine analysis from 59 patients. Mannitol excretion was normal before and after surgery without significant differences between the groups (after operation: 5.4% vs 2.9%, P=0.193). Lactulose and sucrose excretion was within a normal range before surgery and increased afterwards without differences between the groups. IL-6, IL-10, and TNFalpha were elevated after surgery, but there was no difference between the groups [IL-6 (P=0.78), IL-10 (P=0.74), and TNFalpha (P=0.67)]. CONCLUSIONS: Profound haemodilution during normothermic CPB brought about significant changes neither in intestinal permeability nor in cytokine release. It may be concluded that a haematocrit of 19-21% during normothermic CPB does not impair intestinal barrier function and cytokine response in patients without gastrointestinal comorbidity.

Effects of remifentanil and fentanyl on the cell-mediated immune response in patients undergoing elective coronary artery bypass graft surgery.

This prospective randomized pilot study compared the influence of fentanyl-based versus remifentanil-based anaesthesia on cytokine responses and expression of the suppressor of cytokine signalling (SOCS)-3 gene following coronary artery bypass graft surgery. Forty patients were assigned to receive anaesthesia with either intravenous remifentanil (0.3 - 0.6 microg/kg per min; n = 20) or intravenous fentanyl (5 - 10 microg/kg per h; n = 20). Levels of interleukin (IL)-6, IL-10, tumour necrosis factor-alpha and interferon-gamma (IFN-gamma) and the expression of SOCS-3 were measured pre- and post-operatively. The data from 33 of the patients were analysed. The IFN-gamma/IL-10 ratio after concanavalin A stimulation in whole blood cells on post-operative day 1 and SOCS-3 gene expression on post-operative day 2 were significantly lower in the remifentanil group than in the fentanyl group. The time in the intensive care unit was also significantly lower in the remifentanil group. These findings suggest that remifentanil can attenuate the exaggerated inflammatory response that occurs after cardiac surgery with cardiopulmonary bypass. Further clinical trials are required to define the influence of choice of intra-operative opioid on post-operative outcome.