The hemodynamic effects of warm versus room-temperature crystalloid fluid bolus therapy in post-cardiac surgery patients.

INTRODUCTION: The contribution of fluid temperature to the effect of crystalloid fluid bolus therapy (FBT) in post-cardiac surgery patients is unknown. We evaluated the hemodynamic effects of FBT with fluid warmed to 40°C (warm FBT) versus room-temperature fluid. METHODS: In this single centre prospective before-and-after study, we evaluated the effects of 500 ml of warm versus room-temperature compound sodium lactate administered over <30 minutes, in 50 cardiac surgery patients admitted to ICU. We recorded hemodynamics continuous before and for 30 minutes after the first FBT. We defined CI responsiveness (CI-R) as an CI increase >15% of baseline immediately after FBT and effect dissipation if the CI returned to <5% of baseline and MAP responsiveness as >10% increase and dissipation as return to <3 mmHg of baseline. RESULTS: Hypotension (56%) and low CI (40%) typically triggered FBT. Temperature decreased >0.3°C in 13 (52%) patients after room-temperature FBT versus 0 (0%) after warm FBT (p < 0.01). CI and MAP responsiveness was similar (16 [64%] versus 11 [44%], p = 0.15 and 15 [60%] versus 17 [68%], p = 0.77, respectively). Among CI responders, CI increased more with room-temperature FBT (+0.6 [IQR, 0.5-1.1] versus +0.5 [IQR, 0.4-0.6] L/min/m2, p = 0.01). However, dissipation was more common after room-temperature versus warm FBT (9/16 [56%] versus 1/11 [9%], p = 0.02). CONCLUSION: In postoperative cardiac surgery patients, warm FBT preserved core temperature and induced smaller but more sustained CI increases among responders. Fluid temperature appears to impact both core temperature and the duration of CI response.

Glycemic lability index and mortality in critically ill patients-A multicenter cohort study.

BACKGROUND: Emerging evidence indicates a relationship between glycemic variability during intensive care unit (ICU) admission and death. We assessed whether mean glucose, hypoglycemia occurrence, or premorbid glycemic control modified this relationship. METHODS: In this retrospective, multicenter cohort study, we included adult patients admitted to five ICUs in Australia and Sweden with available preadmission glycated hemoglobin A1c (HbA1c) and three or more glucose readings. We calculated the glycemic lability index (GLI), a measure of glycemic variability, and the time-weighted average blood glucose (TWA-BG) from all glucose readings. We used logistic regression analysis with adjustment for hypoglycemia and admission characteristics to assess the independent association of GLI (above vs. below cohort median) and TWA-BG (above vs. below cohort median) with hospital mortality. RESULTS: Among 2305 patients, 859 (37%) had diabetes, median GLI was 40 [mmol/L]2 /h/week, median TWA-BG was 8.2 mmol/L, 171 (7%) developed hypoglycemia, and 371 (16%) died. The adjusted odds ratio for death was 1.61 (95% CI, 1.19-2.15; P = .002) for GLI above versus below median and 1.06 (95% CI, 0.80-1.41; P = .67) for TWA-BG above versus below median. The relationship between GLI and mortality was not modified by TWA-BG (P [interaction] = 0.66), a history of diabetes (P [interaction] = 0.89) or by HbA1c ≥52 mmol/mol (vs. <52 mmol/mol) (P [interaction] = 0.29). CONCLUSION: In adult patients admitted to an ICU in Sweden and Australia, a high GLI was associated with increased hospital mortality irrespective of the level of mean glycemia, hypoglycemia occurrence, or premorbid glycemic control. These findings support the assessment of interventions to reduce glycemic variability during critical illness.

Point-of-care creatinine measurements to predict acute kidney injury.

BACKGROUND: Plasma creatinine (Cr) is a marker of kidney function and typically measured once daily. We hypothesized that Cr measured by point-of-care technology early after ICU admission would be a good predictor of acute kidney injury (AKI) the next day in critically ill patients. METHODS: We conducted a retrospective database audit in a single tertiary ICU database. We included patients with normal first admission Cr (CrF ) and identified a Cr value (CrP ) obtained within 6-12 hours from ICU admission. We used their difference converted into percentage (delta-Cr-%) to predict subsequent AKI (based on Cr and/or need for renal replacement therapy) the next day. We assessed predictive value by calculating area under the receiver characteristic curve (AUC), logistic regression models for AKI with and without delta-Cr-%, and the category-free net reclassifying index (cfNRI). RESULTS: We studied 780 patients. Overall, 70 (9.0%) fulfilled the Cr AKI definition by CrP measurement. On day 2, 148 patients (19.0%) were diagnosed with AKI. AUC (95% CI) for delta-Cr-% to predict AKI on day 2 was 0.82 (95% CI 0.78-0.86), and 0.74 (95% CI 0.69-0.80) when patients with AKI based on the CrP were excluded. Using a cut-off of 17% increment, the positive likelihood ratio (95% CI) for delta-Cr-% to predict AKI was 3.5 (2.9-4.2). The cfNRI was 90.0 (74.9-106.1). CONCLUSIONS: Among patients admitted with normal Cr, early changes in Cr help predict AKI the following day.

Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure.

Reliable estimates of the long-term outcomes of acute kidney injury (AKI) are needed to inform clinical practice and guide allocation of health care resources. This systematic review and meta-analysis aimed to quantify the association between AKI and chronic kidney disease (CKD), end-stage kidney disease (ESKD), and death. Systematic searches were performed through EMBASE, MEDLINE, and grey literature sources to identify cohort studies in hospitalized adults that used standardized definitions for AKI, included a non-exposed comparator, and followed patients for at least 1 year. Risk of bias was assessed by the Newcastle-Ottawa Scale. Random effects meta-analyses were performed to pool risk estimates; subgroup, sensitivity, and meta-regression analyses were used to investigate heterogeneity. Of 4973 citations, 82 studies (comprising 2,017,437 participants) were eligible for inclusion. Common sources of bias included incomplete reporting of outcome data, missing biochemical values, and inadequate adjustment for confounders. Individuals with AKI were at increased risk of new or progressive CKD (HR 2.67, 95% CI 1.99-3.58; 17.76 versus 7.59 cases per 100 person-years), ESKD (HR 4.81, 95% CI 3.04-7.62; 0.47 versus 0.08 cases per 100 person-years), and death (HR 1.80, 95% CI 1.61-2.02; 13.19 versus 7.26 deaths per 100 person-years). A gradient of risk across increasing AKI stages was demonstrated for all outcomes. For mortality, the magnitude of risk was also modified by clinical setting, baseline kidney function, diabetes, and coronary heart disease. These findings establish the poor long-term outcomes of AKI while highlighting the importance of injury severity and clinical setting in the estimation of risk.

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.

Liberal Glucose Control in ICU Patients With Diabetes: A Before-and-After Study.

OBJECTIVES: To assess the feasibility, biochemical efficacy, and safety of liberal versus conventional glucose control in ICU patients with diabetes. DESIGN: Prospective, open-label, sequential period study. SETTING: A 22-bed mixed ICU of a tertiary hospital in Australia. PATIENTS: We compared 350 consecutive patients with diabetes admitted over 15 months who received liberal glucose control with a preintervention control population of 350 consecutive patients with diabetes who received conventional glucose control. INTERVENTIONS: Liberal control patients received insulin therapy if glucose was greater than 14 mmol/L (target: 10-14 mmol/L [180-252 mg/dL]). Conventional control patients received insulin therapy if glucose was greater than 10 mmol/L (target: 6-10 mmol/L [108-180 mg/dL]). MEASUREMENTS AND MAIN RESULTS: We assessed separation in blood glucose, insulin requirements, occurrence of hypoglycemia (blood glucose ≤ 3.9 mmol/L [70 mg/dL]), creatinine and white cell count levels, and clinical outcomes. The median (interquartile range) time-weighted average blood glucose concentration was significantly higher in the liberal control group (11.0 mmol/L [8.7-12.0 mmol/L]; 198 mg/dL [157-216 mg/dL]) than in the conventional control group (9.6 mmol/L [8.5-11.0 mmol/L]; 173 mg/dL [153-198 mg/dL]; p < 0.001). Overall, 132 liberal control patients (37.7%) and 188 conventional control patients (53.7%) received insulin in ICU (p < 0.001). Hypoglycemia occurred in 6.6% and 8.6%, respectively (p = 0.32). Among 314 patients with glycated hemoglobin A1c greater than or equal to 7%, hypoglycemia occurred in 4.1% and 9.6%, respectively (p = 0.053). Trajectories of creatinine and white cell count were similar in the groups. In multivariable analyses, we found no independent association between glucose control and mortality, duration of mechanical ventilation, or ICU-free days to day 30. CONCLUSIONS: In ICU patients with diabetes, during a period of liberal glucose control, insulin administration, and among patients with hemoglobin A1c greater than or equal to 7%, the prevalence of hypoglycemia was reduced, without negatively affecting serum creatinine, the white cell count response, or other clinical outcomes. (Trial Registration: Australian New Zealand Clinical Trials Registry; ACTRN12615000216516).

Erythropoiesis-stimulating Agents in Critically Ill Trauma Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: To perform a meta-analysis of all relevant randomized controlled trials assessing the effect of erythropoiesis-stimulating agents (ESAs) in critically ill trauma patients. BACKGROUND: ESAs have effects beyond erythropoiesis. The administration of the ESA epoetin alfa to critically ill trauma patients has been associated with a reduction in mortality. METHODS: We performed a systematic review and meta-analysis with trial sequential analysis. We searched Medline, Medline in Process, and other nonindexed citations, EMBASE, and the Cochrane Database from inception until September 9, 2015, for randomized controlled trials comparing ESAs to placebo (or no ESA). RESULTS: We identified 9 eligible studies that randomly assigned 2607 critically ill patients after trauma to an ESA or placebo (or no ESA). Compared with placebo (or no ESA), ESA therapy was associated with a substantial reduction in mortality [risk ratio (RR) 0.63, 95% confidence interval (CI) 0.49-0.79, P = 0.0001, I = 0%). In patients with traumatic brain injury, ESA therapy did not increase the number of patients surviving with moderate disability or good recovery (RR 1.00, 95% CI 0.88-1.15, P = 0.95, I = 0%). With the dosing regimens employed in the included studies, ESA therapy did not increase the risk of lower limb proximal deep venous thrombosis (RR 0.97, 95% CI 0.72-1.29, P = 0.78, I = 0%). CONCLUSIONS: The administration of ESAs to critically ill trauma patients is associated with a significant improvement in mortality without an increase in the rate of lower limb proximal deep venous thrombosis. Given the worldwide public health significance of these findings research to validate or refute them is required.

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.

Liberal Versus Conventional Glucose Targets in Critically Ill Diabetic Patients: An Exploratory Safety Cohort Assessment.

OBJECTIVES: To assess the feasibility, safety, and impact on relative hypoglycemia of liberal versus conventional blood glucose concentration targets in critically ill diabetic patients. DESIGN: Prospective, open-label, sequential-period exploratory study. SETTING: A 22-bed multidisciplinary ICU of a tertiary care hospital in Australia. PATIENTS: Eighty adult diabetic patients, 40 from the conventional before period and 40 from the liberal after period. INTERVENTIONS: Blood glucose concentration targets were 6-10 mmol/L during the before period and 10-14 mmol/L during the after period. MEASUREMENTS AND MAIN RESULTS: We used admission glycated hemoglobin to estimate premorbid baseline blood glucose concentration. We defined glycemic distance as the difference between blood glucose concentration in ICU and baseline blood glucose concentration. During the first 48 ICU hours, we recorded absolute (blood glucose concentration, < 3.9 mmol/L) and relative (glycemic distance, > 30% below baseline) hypoglycemia rates, insulin administration, and outcomes. The groups had similar baseline characteristics. We observed a negative glycemic distance in 248 of 488 blood glucose concentrations (50.8%) during the before period and 164 of 485 (33.8%) during the after period (p < 0.001). We detected relative hypoglycemia in 20 (50.0%) and nine (22.5%) patients in the before and after periods, respectively (p = 0.01). On day 1, 50.0% and 16.7% received insulin in the before and after periods (p = 0.007). ICU and hospital length of stay and mortality were similar between groups. CONCLUSIONS: In a safety cohort of critically ill diabetic patients, a blood glucose concentration target of 10-14 mmol/L resulted in fewer episodes of negative glycemic distance or relative hypoglycemia and reduced insulin administration compared with a target of 6-10 mmol/L.

A Pilot Assessment of Carotid and Brachial Artery Blood Flow Estimation Using Ultrasound Doppler in Cardiac Surgery Patients.

OBJECTIVES: To estimate carotid and brachial artery blood flow with Doppler ultrasound in cardiac surgery patients and relate such estimates to cardiac index, lactate levels, and markers of renal function. DESIGN: A prospective observational study. SETTING: A teaching hospital. PARTICIPANTS: Twenty-five elective cardiac surgery patients. INTERVENTIONS: The authors measured bilateral carotid and brachial artery blood flows using Doppler ultrasound and, simultaneously, cardiac index using a pulmonary artery catheter; lactate and serum creatinine levels; and urine output. The relationship between these indices and biomarkers was assessed statistically. MEASUREMENTS AND MAIN RESULTS: Median carotid arterial blood flow was estimated at 0.323 L/min (interquartile ratio [IQR], 0.256-0.429 L/min) on the right and 0.308 L/min (IQR, 0.247-0.376 L/min) on the left at baseline. Median brachial arterial blood flow was estimated at 0.063 L/min (IQR, 0.039-0.115 L/min) on the right and 0.063 L/min (IQR, 0.039-0.081 L/min) on the left at baseline. There was a weak correlation between right- and left-sided flows (brachial: rho = 0.285; carotid: rho = 0.384) and between brachial and carotid flow (right: rho = 0.135, left: rho = 0.225). There also was a weak correlation between cardiac index and brachial flow (right: rho = 0.215; left: rho = 0.320) and carotid flow (left: rho = 0.159) immediately after surgery, and no correlation 1 day after surgery (right brachial: rho = -0.010; left brachial: rho = -0.064; left carotid: rho = -0.060). There were no significant correlations between carotid or brachial flows and lactate and serum creatinine levels or urine output. CONCLUSIONS: In cardiac surgery patients, Doppler-estimated carotid and brachial arterial blood flows have only a weak correlation with cardiac index and no correlation with lactate or creatinine levels or urine output. Thus, Doppler estimation of these blood flows cannot be used to provide noninvasive estimates of cardiac index in patients after cardiac surgery.

Nasal high-flow oxygen therapy in ICU: A before-and-after study.

BACKGROUND: Non-intubated intensive care patients commonly receive supplemental oxygen by high-flow face mask (HFFM), simple face mask (FM) and nasal prongs (NP) during their ICU admission. However, high-flow nasal prongs (HFNP) offer considerable performance capabilities that may sufficiently meet all their oxygen therapy requirements. STUDY AIMS: To assess the feasibility, safety and cost-effectiveness of introducing a protocol in which HFNP was the primary oxygen delivery device for non-intubated intensive care patients. METHOD: Prospective 4-week before-and-after study (6 months apart) for all adult patients admitted to a 22-bed tertiary ICU in Melbourne, Australia. RESULTS: 117 patients (57 before, 60 after) were included: 86 (73.5%) received mechanical ventilation. Feasibility revealed a significant reduction in HFFM (52.6-0%, p<.001), FM (35.1-8.3%, p=.002) and NP (75.4-36.7%, p<.001) use and an increase in HFNP use (31.6-81.7%, p<.05) during the after period. Following extubation, there was a significant reduction in HFFM use (65.7% vs. 0%, p<.05) and an increase HFNP use (8.6% vs. 87.5%, p<.05). Costing was in favour of the after period with a consumable cost saving per patient (AUD $32.56 vs. $17.62, p<.05). During the after period, more patients were discharged from ICU with HFNP than during the before period (5 vs. 33 patients, p<.05) and fewer patients (5 vs. 14 patients) used three or more oxygen delivery devices. Safety outcomes demonstrated no significant difference in the number of intubations, re-intubations, readmissions or non-invasive ventilation use between the two time periods. CONCLUSIONS: Using HFNP as the primary oxygen delivery method for non-intubated intensive care patients was feasible, appeared safe, and the oxygen device costs were reduced. The findings of our single-centre study support further multi-centre evaluations of HFNP therapy protocols in non-ventilated intensive care patients.

Fluid Bolus Therapy-Based Resuscitation for Severe Sepsis in Hospitalized Children: A Systematic Review.

OBJECTIVES: To review systematically data from randomized and nonrandomized studies of fluid bolus therapy in hospitalized children with septic shock. DATA SOURCES: Medline, EMBASE, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: We searched for randomized controlled studies of fluid bolus therapy in children with severe sepsis. We identified retrospective, prospective, and observational studies. We excluded studies of severe sepsis/septic shock due to a specific microbiological etiology, neonatal studies, and studies where advanced supportive therapies were unavailable. DATA EXTRACTION: Two authors screened articles for inclusion. DATA SYNTHESIS: We identified and analyzed three randomized controlled trials and eight nonrandomized studies. Heterogeneity precluded meta-analysis. Two single-center Indian studies and one Brazilian study assessed three different fluid bolus therapy regimens in small cohorts with different populations, physiological triggers, and physiological and clinical outcomes. No randomized controlled trials compared fluid bolus therapy with alternative interventions, such as vasopressors. The nonrandomized studies were heterogeneous in populations, methodology, and outcome measures. No observed physiological differences were identified based on volume of fluid bolus therapy. CONCLUSIONS: There are only limited data to support the use of fluid bolus therapy in hospitalized children. Prospective observational data and randomized controlled trials are urgently needed to evaluate this therapy in resource rich settings.

Urinary Neutrophil Gelatinase-Associated Lipocalin as Predictor of Short- or Long-Term Outcomes in Cardiac Surgery Patients.

OBJECTIVES: To determine the ability of urinary neutrophil gelatinase-associated lipocalin (uNGAL) to predict cardiac surgery-associated acute kidney injury (CSA-AKI), continuous renal replacement therapy (CRRT), mortality, and a composite outcome of major adverse kidney events at 365 days (MAKE365), and to investigate the influence of cardiopulmonary bypass (CPB) on NGAL release. DESIGN: A prospective observational study. SETTING: A single-center university hospital. PARTICIPANTS: A cohort of 288 adult cardiac surgery patients. INTERVENTIONS: uNGAL was measured at baseline, immediately after surgery, and on days 1 and 2 postoperatively. The authors used the recent Kidney Disease Improving Global Outcomes consensus criteria to define CSA-AKI. MEASUREMENTS AND MAIN RESULTS: CSA-AKI occurred in 36.1% of patients. uNGAL rapidly became significantly higher in patients who developed AKI, with peak value immediately after surgery (349.9 [76.6-1446.6] v 90.1 [20.8-328] ng/mg creatinine; p<0.001). No measure of uNGAL (peak, postsurgery, day 1 or 2 postsurgery) accurately predicted CSA-AKI, CRRT, mortality, or MAKE365. However, immediately after surgery, CPB induced greater uNGAL release compared with off-pump surgery (265.5 µmol/L [71-989.6] v 48.7 ng/mg creatinine [17-129.8]; p<0.001). Moreover, such early uNGAL release correlated with CPB duration (r = 0.505; p<0.001) but not with peak serum creatinine values on day 3 or 7 after surgery. CONCLUSIONS: uNGAL had a limited predictive ability for CSA-AKI or other relevant clinical outcomes after cardiac surgery and appeared to be more closely related to the use and duration of CPB. Thus, its levels may represent the aggregate effect of an inflammatory response to CPB as well as a renal response to cardiac surgery and inflammation.

Stress hyperlactatemia modifies the relationship between stress hyperglycemia and outcome: a retrospective observational study.

OBJECTIVE: To study the effect of stress hyperlactatemia on the association between stress hyperglycemia and mortality. DESIGN: Retrospective cross-sectional observation study. SETTING: Three ICUs using arterial blood gases with simultaneous glucose and lactate measurements during ICU stay. PATIENTS: Cohort of 7,925 consecutive critically ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 152,349 simultaneous measurements of glucose and lactate. We performed multivariable analysis to study the association of different metrics of glucose and lactate with hospital mortality. On day 1, first (p = 0.013), highest (p = 0.001), mean (p = 0.019), and time-weighted mean (p = 0.010) glucose levels were associated with increased mortality. A similar, but stronger, association was seen for corresponding lactate metrics (p < 0.0001 for all). However, once glucose and lactate metrics were entered into the multivariable logistic regression model simultaneously, all measures of glycemia ceased to be significantly associated with hospital mortality regardless of the metrics being used (first, highest, mean, time-weighed; p > 0.05 for all), whereas all lactate metrics remained associated with mortality (p < 0.0001 for all). In patients with at least one episode of moderate hypoglycemia (glucose ≤ 3.9 mmol/L), glucose metrics were not associated with mortality when studied separately (p > 0.05 for all), whereas lactate was (p < 0.05 for all), but when incorporated into a model simultaneously, highest glucose on day 1 was associated with mortality (p< 0.05), but not other glucose metrics (p > 0.05), whereas all lactate metrics remained associated with mortality (p < 0.05 for all). CONCLUSIONS: Stress hyperlactatemia modifies the relationship between hyperglycemia and mortality. There is no independent association between hyperglycemia and mortality once lactate levels are considered.

Conservative oxygen therapy in mechanically ventilated patients: a pilot before-and-after trial.

OBJECTIVES: To assess the feasibility and safety of a conservative approach to oxygen therapy in mechanically ventilated ICU patients. DESIGN: Pilot prospective before-and-after study. SETTING: A 22-bed multidisciplinary ICU of a tertiary care hospital in Australia. PATIENTS: A total of 105 adult (18 years old or older) patients required mechanical ventilation for more than 48 hours: 51 patients during the "conventional" before period and 54 after a change to "conservative" oxygen therapy. INTERVENTIONS: Implementation of a conservative approach to oxygen therapy (target SpO2 of 90-92%). MEASUREMENTS AND MAIN RESULTS: We collected 3,169 datasets on 799 mechanical ventilation days. During conservative oxygen therapy the median time-weighted average SpO2 on mechanical ventilation was 95.5% (interquartile range, 94.0-97.3) versus 98.4% (97.3-99.1) (p < 0.001) during conventional therapy. The median PaO2 was 83 torr (71-94) versus 107 torr (94-131) (p < 0.001) with a change to a median FIO2 of 0.27 (0.24-0.30) versus 0.40 (0.35-0.44) (p < 0.001). Conservative oxygen therapy decreased the median total amount of oxygen delivered during mechanical ventilation by about two thirds (15,580 L [8,263-29,351 L] vs 5,122 L [1,837-10,499 L]; p < 0.001). The evolution of the PaO2/FIO2 ratio was similar during the two periods, and there were no difference in any other biochemical or clinical outcomes. CONCLUSIONS: Conservative oxygen therapy in mechanically ventilated ICU patients was feasible and free of adverse biochemical, physiological, or clinical outcomes while allowing a marked decrease in excess oxygen exposure. Our study supports the safety and feasibility of future pilot randomized controlled trials of conventional compared with conservative oxygen therapy.

Physiological changes after fluid bolus therapy in sepsis: a systematic review of contemporary data.

Fluid bolus therapy (FBT) is a standard of care in the management of the septic, hypotensive, tachycardic and/or oliguric patient. However, contemporary evidence for FBT improving patient-centred outcomes is scant. Moreover, its physiological effects in contemporary ICU environments and populations are poorly understood. Using three electronic databases, we identified all studies describing FBT between January 2010 and December 2013. We found 33 studies describing 41 boluses. No randomised controlled trials compared FBT with alternative interventions, such as vasopressors. The median fluid bolus was 500 ml (range 100 to 1,000 ml) administered over 30 minutes (range 10 to 60 minutes) and the most commonly administered fluid was 0.9% sodium chloride solution. In 19 studies, a predetermined physiological trigger initiated FBT. Although 17 studies describe the temporal course of physiological changes after FBT in 31 patient groups, only three studies describe the physiological changes at 60 minutes, and only one study beyond this point. No studies related the physiological changes after FBT with clinically relevant outcomes. There is a clear need for at least obtaining randomised controlled evidence for the physiological effects of FBT in patients with severe sepsis and septic shock beyond the period immediately after its administration.

Current ventilation practice during general anaesthesia: a prospective audit in Melbourne, Australia.

BACKGROUND: Recent evidence suggests that the use of low tidal volume ventilation with the application of positive end-expiratory pressure (PEEP) may benefit patients at risk of respiratory complications during general anaesthesia. However current Australian practice in this area is unknown. METHODS: To describe current practice of intraoperative ventilation with regard to tidal volume and application of PEEP, we performed a multicentre audit in patients undergoing general anaesthesia across eight teaching hospitals in Melbourne, Australia. RESULTS: We obtained information including demographic characteristics, type of surgery, tidal volume and the use of PEEP in a consecutive cohort of 272 patients. The median age was 56 (IQR 42-69) years; 150 (55%) were male. Most common diagnostic groups were general surgery (31%), orthopaedic surgery (20%) and neurosurgery (9.6%). Mean FiO2 was 0.6 (IQR 0.5-0.7). Median tidal volume was 500 ml (IQR 450-550). PEEP was used in 54% of patients with a median value of 5.0 cmH2O (IQR 4.0-5.0) and median tidal volume corrected for predicted body weight was 9.5 ml/kg (IQR 8.5-10.4). Median peak inspiratory pressure was 18 cmH2O (IQR 15-22). In a cohort of patients considered at risk for respiratory complications, the median tidal volume was still 9.8 ml/kg (IQR 8.6-10.7) and PEEP was applied in 66% of patients with a median value of 5 cmH20 (IQR 4-5). On multivariate analyses positive predictors of tidal volume size included male sex (p < 0.01), height (p = 0.04) and weight (p < 0.001). Positive predictors of the use of PEEP included surgery in a tertiary hospital (OR = 3.11; 95% CI: 1.05 to 9.23) and expected prolonged duration of surgery (OR = 2.47; 95% CI: 1.04 to 5.84). CONCLUSION: In mechanically ventilated patients under general anaesthesia, tidal volume was high and PEEP was applied to the majority of patients, but at modest levels. The findings of our study suggest that the control groups of previous randomized controlled trials do not closely reflect the practice of mechanical ventilation in Australia.

The microbiological and clinical outcome of guide wire exchanged versus newly inserted antimicrobial surface treated central venous catheters.

INTRODUCTION: The management of suspected central venous catheter (CVC)-related sepsis by guide wire exchange (GWX) is not recommended. However, GWX for new antimicrobial surface treated (AST) triple lumen CVCs has never been studied. We aimed to compare the microbiological outcome of triple lumen AST CVCs inserted by GWX (GWX-CVCs) with newly inserted triple lumen AST CVCs (NI-CVCs). METHODS: We studied a cohort of 145 consecutive patients with GWX-CVCs and contemporaneous site-matched control cohort of 163 patients with NI-CVCs in a tertiary intensive care unit (ICU). RESULTS: GWX-CVC and NI-CVC patients were similar for mean age (58.7 vs. 62.2 years), gender (88 (60.7%) vs. 98 (60.5%) male) and illness severity on admission (mean Acute Physiology and Chronic Health Evaluation (APACHE) III: 71.3 vs. 72.2). However, GWX patients had longer median ICU lengths of stay (12.2 vs. 4.4 days; P < 0.001) and median hospital lengths of stay (30.7 vs. 18.0 days; P < 0.001). There was no significant difference with regard to the number of CVC tips with bacterial or fungal pathogen colonization among GWX-CVCs vs. NI-CVCs (5 (2.5%) vs. 6 (7.4%); P = 0.90). Catheter-associated blood stream infection (CA-BSI) occurred in 2 (1.4%) GWX patients compared with 3 (1.8%) NI-CVC patients (P = 0.75). There was no significant difference in hospital mortality (35 (24.1%) vs. 48 (29.4%); P = 0.29). CONCLUSIONS: GWX-CVCs and NI-CVCs had similar rates of tip colonization at removal, CA-BSI and mortality. If the CVC removed by GWX is colonized, a new CVC must then be inserted at another site. In selected ICU patients at higher central vein puncture risk receiving AST CVCs GWX may be an acceptable initial approach to line insertion.

Breaches of pre-medical emergency team call criteria in an Australian hospital.

Objectives and outcomes: To evaluate the 24hrs before medical emergency team (MET) calls to examine: 1) the frequency, nature, and timing of pre-MET criteria breaches; 2) differences in characteristics and outcomes between patients who did and didn't experience pre-MET breaches. Design: Retrospective observational study November 2020-June 2021. Setting: Tertiary referral Australian hospital. Participants: Adults (≥18 years) experiencing MET calls. Results: Breaches in pre-MET criteria occurred prior to 1886/2255 (83.6%) MET calls, and 1038/1281 (81.0%) of the first MET calls. Patients with pre-MET breaches were older (median [IQR] 72 [57-81] vs 66 [56-77] yrs), more likely to be admitted from home (87.8% vs 81.9%) and via the emergency department (73.0% vs 50.2%), but less likely to be for full resuscitation after (67.3% vs 76.5%) the MET. The three most common pre-MET breaches were low SpO2 (48.0%), high pulse rate (39.8%), and low systolic blood pressure (29.0%) which were present for a median (IQR) of 15.4 (7.5-20.8), 13.2 (4.3-21.0), and 12.6 (3.5-20.1) hrs before the MET call, respectively. Patients with pre-MET breaches were more likely to need intensive care admission within 24 h (15.6 vs 11.9%), have repeat MET calls (33.3 vs 24.7%), and die in hospital (15.8 vs 9.9%). Conclusions: Four-fifths of MET calls were preceded by pre-MET criteria breaches, which were present for many hours. Such patients were older, had more limits of treatment, and experienced worse outcomes. There is a need to improve goals of care documentation and pre-MET management of clinical deterioration.