A Pilot Randomized Controlled Study of Mild Hypercapnia During Cardiac Surgery With Cardiopulmonary Bypass.

OBJECTIVES: To test whether targeted therapeutic mild hypercapnia (TTMH) would attenuate cerebral oxygen desaturation detected using near-infrared spectroscopy during cardiac surgery requiring cardiopulmonary bypass (CPB). DESIGN: Randomized controlled trials. SETTING: Operating rooms and intensive care unit of tertiary hospital. PARTICIPANTS: The study comprised 30 patients undergoing cardiac surgery with CPB. INTERVENTIONS: Patients were randomly assigned to receive either standard carbon dioxide management (normocapnia) or TTMH (target arterial carbon dioxide partial pressure between 50 and 55 mmHg) throughout the intraoperative period and postoperatively until the onset of spontaneous ventilation. MEASUREMENTS AND MAIN RESULTS: Relevant biochemical and hemodynamic variables were measured, and cerebral tissue oxygen saturation (SctO2) was monitored with near-infrared spectroscopy. Patients were followed-up with neuropsychological testing. Patient demographics between groups were compared using the Fisher exact and Mann-Whitney tests, and SctO2 between groups was compared using repeated measures analysis of variance. The median patient age was 67 years (interquartile range [IQR] 62-72 y), and the median EuroSCORE II was 1.1. The median CPB time was 106 minutes. The mean intraoperative arterial carbon dioxide partial pressure for each patient was significantly higher with TTMH (52.1 mmHg [IQR 49.9-53.9 mmHg] v 40.8 mmHg [IQR 38.7-41.7 mmHg]; p < 0.001) as was pulmonary artery pressure (23.9 mmHg [IQR 22.4-25.3 mmHg] v 18.5 mmHg [IQR 14.8-20.7 mmHg]; p = 0.004). There was no difference in mean percentage change in SctO2 during CPB in the control group for both hemispheres (left: -6.7% v -2.3%; p = 0.110; right: -7.9% v -1.0%; p = 0.120). Compliance with neuropsychological test protocols was poor. However, the proportion of patients with drops in test score >20% was similar between groups in all tests. CONCLUSIONS: TTMH did not increase SctO2 appreciably during CPB but increased pulmonary artery pressures before and after CPB. These findings do not support further investigation of TTMH as a means of improving SctO2 during and after cardiac surgery requiring CPB.

Near-Infrared Spectroscopy in Adult Cardiac Surgery Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: To identify the normal baseline preoperative range of cerebral tissue oxygen saturation (SctO2) derived using near-infrared spectroscopy (NIRS) and the efficacy of perioperative interventions designed to modulate SctO2 in cardiac surgical patients. DESIGN: Systematic review and meta-analysis of relevant randomized controlled trials (RCTs) extracted from the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. SETTING: Hospitals performing cardiac surgery. PARTICIPANTS: The study comprised 953 participants from 11 RCTs. INTERVENTIONS: Interventions included the following: (1) SctO2 monitoring protocol compared with no monitoring; (2) use of cardiopulmonary bypass (CPB) compared with no CPB; (3) normothermic CPB compared with hypothermic CPB; (4) glyceryl trinitrate during surgery compared with placebo; (5) midazolam during induction of anesthesia compared with propofol; (6) sevoflurane anesthesia compared with total intravenous anesthesia; (7) sevoflurane anesthesia compared with propofol-based anesthesia; and (8) norepinephrine during CPB compared with phenylephrine. MEASUREMENTS AND MAIN RESULTS: Eleven RCTs with 953 participants measured baseline preoperative SctO2 using NIRS. The pooled mean baseline SctO2 was 66.4% (95% CI 65.0-67.7), generating a reference range of 51.0% to 81.8%. Four interventions (1, 3, 4, and 6 described in the Interventions section above) increased intraoperative SctO2 across the majority of reported time points. Postoperative follow-up of SctO2 occurred in only 1 study, and postoperative cognitive assessment correlating SctO2 with cognitive function was applied in only 4 studies using variable methodology. CONCLUSIONS: The authors have established that reference values for baseline NIRS-derived SctO2 in cardiac surgery patients are varied and have identified interventions that modulate SctO2. This information opens the door to standardized research and interventional studies in this field.

Initial and extended use of femoral versus nonfemoral double-lumen vascular catheters and catheter-related infection during continuous renal replacement therapy.

BACKGROUND: The risk of catheter-related infection or bacteremia, with initial and extended use of femoral versus nonfemoral sites for double-lumen vascular catheters (DLVCs) during continuous renal replacement therapy (CRRT), is unclear. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Critically ill patients on CRRT in a combined intensive care unit of a tertiary institution. FACTOR: Femoral versus nonfemoral venous DLVC placement. OUTCOMES: Catheter-related colonization (CRCOL) and bloodstream infection (CRBSI). MEASUREMENTS: CRCOL/CRBSI rates expressed per 1,000 catheter-days. RESULTS: We studied 458 patients (median age, 65 years; 60% males) and 647 DLVCs. Of 405 single-site only DLVC users, 82% versus 18% received exclusively 419 femoral versus 82 jugular or subclavian DLVCs, respectively. The corresponding DLVC indwelling duration was 6±4 versus 7±5 days (P=0.03). Corresponding CRCOL and CRBSI rates (per 1,000 catheter-days) were 9.7 versus 8.8 events (P=0.8) and 1.2 versus 3.5 events (P=0.3), respectively. Overall, 96 patients with extended CRRT received femoral-site insertion first with subsequent site change, including 53 femoral guidewire exchanges, 53 new femoral venipunctures, and 47 new jugular/subclavian sites. CRCOL and CRBSI rates were similar for all such approaches (P=0.7 and P=0.9, respectively). On multivariate analysis, CRCOL risk was higher in patients older than 65 years and weighing >90kg (ORs of 2.1 and 2.2, respectively; P<0.05). This association between higher weight and greater CRCOL risk was significant for femoral DLVCs, but not for nonfemoral sites. Other covariates, including initial or specific DLVC site, guidewire exchange versus new venipuncture, and primary versus secondary DLVC placement, did not significantly affect CRCOL rates. LIMITATIONS: Nonrandomized retrospective design and single-center evaluation. CONCLUSIONS: CRCOL and CRBSI rates in patients on CRRT are low and not influenced significantly by initial or serial femoral catheterizations with guidewire exchange or new venipuncture. CRCOL risk is higher in older and heavier patients, the latter especially so with femoral sites.

Non-invasive continuous haemodynamic monitoring and response to intervention in haemodynamically unstable patients during rapid response team review.

INTRODUCTION: During rapid response team (RRT) management of haemodynamic instability (HI), continuous non-invasive haemodynamic monitoring may provide supplemental physiological information. OBJECTIVES: To continuously and non-invasively obtain the cardiac index (CI) and mean arterial pressure (MAP) in patients with HI at baseline and during RRT management using the ClearSight™ device. METHODS: We performed a prospective observational study in adult patients managed by the RRT for tachycardia or hypotension or both. We assessed changes from baseline in heart rate (HR), MAP, CI, stroke volume index (SVI) and systemic vascular resistance index (SVRI) (i) at 5-minutely intervals up to 20 min, and (ii) over the entire 20-min period. We analysed patients by RRT trigger (tachycardia/hypotension) and intervention (fluid bolus therapy [FBT]/ no FBT). RESULTS: We successfully recorded the CI in 47 of 50 (94%) patients. RRT reviews triggered by hypotension rather than tachycardia had a lower baseline HR (-45.4 bpm, p = <0.0001), MAP (-16.1 mmHg, p = 0.0007) and CI (1.0 L/min/m2, p = 0.0025). Compared to baseline, in the tachycardia group, there was a small increase in MAP overall and at the 15-20 min time-block from 83.2 mmHg to 87.1 mmHg (+3.9 mmHg, p = 0.0066) and 85.5 mmHg (+2.3 mmHg, p = 0.0061), respectively. In those who received FBT, there was a statistically significant increase in MAP overall and at the 15-20 min time-block compared to baseline, from 70.1 mmHg to 73.5 mmHg (+3.4 mmHg, p = 0.0036) and 74.3 mmHg (+4.2 mmHg, p = 0.0037), respectively. However, there were no statistically significant changes in mean HR, CI, SVI, or SVRI when comparing baseline to the entire 20-min period or 5-min time-blocks within any group. CONCLUSIONS: Continuous non-invasive measurement of haemodynamics during RRT management for HI was possible for 20 min. Patients with hypotension rather than tachycardia had lower baseline HR, MAP and CI values. There was a statistically significant but small increase in MAP at the 15-20 min time-block and overall, for both the tachycardia and FBT groups.

Rapid response team review of hemodynamically unstable ward patients: The accuracy of cardiac index assessment.

PURPOSE: Intensive care doctors commonly attend rapid response team (RRT) reviews of hospital-ward patients with hemodynamic instability and estimate the patient's likely cardiac index (CI). We aimed to non-invasively measure the CI of such patients and assess the level of agreement between such measurements and clinically estimated CI categories (low <2L/min/m2, normal 2-2.99L/min/m2 or high ≥3L/min/m2). MATERIALS AND METHODS: A prospective, observational study of non-invasive measurement and clinical estimation of CI categories in 50 adult hospital-ward patients who activated the RRT for 'hemodynamic instability' (tachycardia > 100BPM or hypotension < 90mmHg or both). RESULTS: The CI was measured in 47/50(94%) patients and the mean CI was 3.5(95% CI 3.2-3.7) L/min/m2. Overall, 30(64%) patients had a high CI, 13(28%) and 4(9%) had a normal and a low CI, respectively. The level of agreement between measured and clinically estimated CI categories was low(19.2%). Sensitivity and positive predictive values of clinical estimation were low(0% and 3.3% for high CI, and 0% and 50% for low CI, respectively). CONCLUSIONS: Non-invasive CI measurement was possible in almost all hospital-ward patients triggering RRT review for hemodynamic instability. In such patients, the CI was high, and intensive care clinicians were unable to identify a low or a high CI state.

Conservative versus conventional oxygen therapy for cardiac surgical patients: A before-and-after study.

Avoiding hypoxaemia is considered crucial in cardiac surgery patients admitted to the intensive care unit (ICU). However, avoiding hyperoxaemia may also be important. A conservative approach to oxygen therapy may reduce exposure to hyperoxaemia without increasing the risk of hypoxaemia. Using a before-and-after design, we evaluated the introduction of conservative oxygen therapy (target SpO2 88%-92% using the lowest FiO2) for cardiac surgical patients admitted to the ICU. We studied 9041 arterial blood gas (ABG) datasets: 4298 ABGs from 245 'conventional' and 4743 ABGs from 298 'conservative' oxygen therapy patients. During mechanical ventilation (MV) and while in the ICU, compared to the conventional group, conservative group patients had significantly lower FiO2 exposure and PaO2 values ( P < 0.001 for each). Accordingly, using the mean PaO2 during MV, more conservative group patients were classified as normoxaemic (226 versus 62 patients, P < 0.01), fewer as hyperoxaemic (66 versus 178 patients, P < 0.01) and no patient in either group as hypoxaemic or severely hypoxaemic. Moreover, more ABG samples were hyperoxaemic or severely hyperoxaemic during conventional treatment ( P < 0.001). Finally, there was no difference in ICU or hospital length of stay, ICU or hospital mortality or 30-day mortality between the groups. Our findings support the feasibility and physiological safety of conservative oxygen therapy in patients admitted to ICU after cardiac surgery.

Interobserver agreement for post mortem renal histopathology and diagnosis of acute tubular necrosis in critically ill patients.

BACKGROUND: The renal histopathology of critically ill patients dying with acute kidney injury (AKI) in intensive care units of high income countries remains uncertain. METHODS: Retrospective observational assessment of interobserver agreement in the reporting of renal post mortem histopathology, and the ability of pathologists blinded to the clinical context to independently identify the presence of pre-mortem AKI from digital images of histological sections from 34 critically ill patients dying in teaching hospitals in Australia and Canada. RESULTS: We identified a heterogeneous cohort with a median age of 65 years (interquartile range [IQR], 56.5-77), APACHE II score of 27 (IQR, 19-33), and sepsis as the most common admission diagnosis (12/34; 35%). The most common proximate causes of death were cardiovascular (19/34; 56%) and respiratory (7/34; 21%) failure. AKI was common, with 23 patients (68%) developing RIFLE-F AKI, and 21 patients (62%) receiving renal replacement therapy. Structured reporting for tubular inflammation showed excellent agreement (kappa = 1), but no other subdomain demonstrated better than moderate agreement (kappa < 0.6). Only fair agreement (55.9% of cases; kappa = 0.23) was demonstrated on the diagnosis of moderate to severe acute tubular necrosis (ATN). Pathologist A predicted RIFLE-I or worse AKI with the diagnosis of ATN, with an overall accuracy of 61.8%; pathologist B predicted AKI with an accuracy of 35.3%. CONCLUSIONS: Post mortem assessment of the renal histopathology in critically ill patients is neither robust nor reproducible; independent pathologists agree poorly on the diagnosis of ATN, and their structural assessment appears dissociated from ante-mortem renal function.

Mean arterial pressure and mean perfusion pressure deficit in septic acute kidney injury.

BACKGROUND: Changes in mean perfusion pressure (MPP) from premorbid resting values may contribute to the progression of septic acute kidney injury (AKI). OBJECTIVES: In patients with septic shock, we aimed to investigate the association of changes from premorbid values with AKI severity and progression. METHODS: We obtained premorbid resting mean arterial pressure (MAP), central venous pressure (CVP), and MPP, and then recorded data from intensive care unit admission 2 hourly for the first 24 hours to calculate hemodynamic deficits. We recorded 4-hourly creatinine measurements for 96 hours. The association of hemodynamic variables with progression of AKI by Kidney Disease: Improving Global Outcomes ≥2 stages was explored by multivariate logistic regression. RESULTS: Of 107 patients, 55 (51.4%) had severe AKI. Median MAP deficit was similar for patients with or without severe AKI. Median MPP deficit was 29% in patients with severe AKI and 24% in those without (P = .04), a difference determined by greater CVP levels. Central venous pressure was independently associated with worsening AKI (odds ratio, 1.26 [95% confidence interval, 1.01-1.58]; P = .04). CONCLUSIONS: Mean arterial pressure and MPP deficits were substantial in septic shock patients, with patients with severe AKI having a greater MPP deficit. However, only CVP was independently associated with AKI progression. These findings suggest a possible role for venous congestion in septic AKI.

Haemodynamic and biochemical responses to fluid bolus therapy with human albumin solution, 4% versus 20%, in critically ill adults.

BACKGROUND: Fluid bolus therapy (FBT) is common in critically ill patients. With the exception of use in patients with traumatic brain injury, FBT with human albumin solution (HAS) appears safe and perhaps superior in severe sepsis. OBJECTIVE: To determine the physiological effects of FBT with 4% v 20% HAS. DESIGN, SETTING AND PARTICIPANTS: A retrospective observational study of 202 critically ill patients receiving FBT with HAS in a tertiary intensive care unit between April 2012 and March 2013. METHODS: FBT was instituted with 4% or 20% HAS, according to clinician preference. MAIN OUTCOME MEASURES: We compared biochemical and haemodynamic data between groups at baseline and at 1, 2 and 4 hours after FBT. RESULTS: Patients who had received 20% HAS had more liver disease, a greater need for renal replacement therapy and higher Acute Physiology and Chronic Health Evaluation III scores on admission. Patients who had received 4% HAS received a median volume of 500 mL (interquartile range [IQR], 350-500 mL), compared with 100mL (IQR, 100- 200 mL) in the 20% HAS group (P < 0.0001); a median of 70 mmol v 10 mmol of sodium (P < 0.0001); and a median of 64 mmol v 2 mmol of chloride (P < 0.0001). There was a trend toward higher mean arterial pressures in the 20% group after FBT (78.2 mmHg v 76.4 mmHg, P = 0.03). There were no significant differences in the absolute or percentage change for any haemodynamic parameters. Serum biochemical test results were comparable with a non-significant signal of higher serum chloride and more negative base excess in patients receiving 4% HAS. CONCLUSIONS: Haemodynamically, FBT with 100mL of 20% HAS performs in an equivalent way to 500 mL of 4% HAS but delivers much less fluid, sodium and chloride.