Antoine G. Schneider

Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest

BACKGROUND Arterial carbon dioxide tension (PaCO2) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) after cardiac arrest (CA) has not been evaluated. METHODS AND RESULTS Observational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO2 and propensity score. We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO2 (obtained within 24 h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO2<35 mmHg), 6705 (40.5%) into the normo- (35-45 mmHg) and 6827 (41.3%) into the hypercapnia (>45 mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 [95% CI 1.00-1.24, p=0.04]), lower rate of discharge home (OR 0.81 [0.70-0.94, p<0.01]) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 [1.10-1.37, p<0.001]). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 [0.97-1.15, p=0.19]) but higher rate of discharge home among survivors (OR 1.16 [1.03-1.32, p=0.01]) and similar likelihood of fulfilling the composite outcome (OR 0.97 [0.89-1.06, p=0.52]). Cox-proportional hazards modelling supported these findings. CONCLUSIONS Hypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors.

Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis.

PURPOSE The purpose of the study was to determine the effects of Plasma-Lyte 148 (PL) vs 0.9% saline (NS) fluid resuscitation in diabetic ketoacidosis (DKA). METHODS A multicenter retrospective analysis of adults admitted for DKA to the intensive care unit, who received almost exclusively PL or NS infusion up until 12 hours, was performed. RESULTS Nine patients with PL and 14 patients with NS were studied. Median serum bicarbonate correction was higher in the PL vs NS groups at 4 to 6 hours (8.4 vs 1.7 mEq/L) and 6 to 12 hours (12.8 vs 6.2 mEq/L) from baseline (P < .05). Median standard base excess improved by 10.5 vs 4.2 mEq/L at 4 to 6 hours and by 16.0 vs 9.1 mEq/L at 6 to 12 hours in the PL and NS groups, respectively (P < .05). Chloride levels increased significantly in the NS vs PL groups over 24 hours. Potassium levels were lower at 6 to 12 hours in the PL group. Mean arterial blood pressure was higher at 2 to 4 hours in the PL group, whereas cumulative urine output was lower at 4 to 6 hours in the NS group. There were no differences in glycemic control or duration of intensive care unit stay. CONCLUSION Patients with DKA resuscitated with PL instead of NS had faster initial resolution of metabolic acidosis and less hyperchloremia, with a transiently improved blood pressure profile and urine output.

Acute kidney injury in sepsis

Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease.

Bicarbonate in diabetic ketoacidosis - a systematic review

ObjectiveThis study was designed to examine the efficacy and risk of bicarbonate administration in the emergent treatment of severe acidemia in diabetic ketoacidosis (DKA).MethodsPUBMED database was used to identify potentially relevant articles in the pediatric and adult DKA populations. DKA intervention studies on bicarbonate administration versus no bicarbonate in the emergent therapy, acid-base studies, studies on risk association with cerebral edema, and related case reports, were selected for review. Two reviewers independently conducted data extraction and assessed the citation relevance for inclusion.ResultsFrom 508 potentially relevant articles, 44 were included in the systematic review, including three adult randomized controlled trials (RCT) on bicarbonate administration versus no bicarbonate in DKA. We observed a marked heterogeneity in pH threshold, concentration, amount, and timing for bicarbonate administration in various studies. Two RCTs demonstrated transient improvement in metabolic acidosis with bicarbonate treatment within the initial 2 hours. There was no evidence of improved glycemic control or clinical efficacy. There was retrospective evidence of increased risk for cerebral edema and prolonged hospitalization in children who received bicarbonate, and weak evidence of transient paradoxical worsening of ketosis, and increased need for potassium supplementation. No studies involved patients with an initial pH < 6.85.ConclusionsThe evidence to date does not justify the administration of bicarbonate for the emergent treatment of DKA, especially in the pediatric population, in view of possible clinical harm and lack of sustained benefits.

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.

Bench-to-bedside review: Contrast enhanced ultrasonography - a promising technique to assess renal perfusion in the ICU

Acute kidney injury (AKI) is common in critically ill patients and associated with important morbidity and mortality. Although alterations in renal perfusion are thought to play a causative role in the pathogenesis of AKI, there is, to date, no reliable technique that allows the assessment of renal perfusion that is applicable in the ICU. Contrast-enhanced ultrasound (CEUS) is an ultrasound imaging technique that makes use of microbubble-based contrast agents. These microbubbles, when injected into the bloodstream, allow visualization of vascular structures and, with contrast-specific imaging modes, detection of blood flow at the capillary level. Some recent CEUS-derived approaches allow quantification of blood flow in several organs, including the kidney. Current generation ultrasound contrast agents have strong stability and safety profiles. Along with post-marketing surveillance, numerous studies report safe administration of these agents, including in critically ill patients. This review presents information on the physical principles underlying CEUS, the methods allowing blood flow quantification and the potential applications of CEUS in critical care nephrology, currently as a research tool but perhaps in the future as a way of monitoring renal perfusion.

Clinical review: Optimal dose of continuous renal replacement therapy in acute kidney injury.

Continuous renal replacement therapy (CRRT) is the preferred treatment for acute kidney injury in intensive care units (ICUs) throughout much of the world. Despite the widespread use of CRRT, controversy and center-specific practice variation in the clinical application of CRRT continue. In particular, whereas two single-center studies have suggested survival benefit from delivery of higher-intensity CRRT to patients with acute kidney injury in the ICU, other studies have been inconsistent in their results. Now, however, two large multi-center randomized controlled trials - the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study and the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study - have provided level 1 evidence that effluent flow rates above 25 mL/kg per hour do not improve outcomes in patients in the ICU. In this review, we discuss the concept of dose of CRRT, its relationship with clinical outcomes, and what target optimal dose of CRRT should be pursued in light of the high-quality evidence now available.

Estimation of fluid status changes in critically ill patients: fluid balance chart or electronic bed weight?

PURPOSE Monitoring of fluid balance (FB) can be achieved by subtracting recorded fluid output from input or by measuring changes in body weight (BW). The latter approach is difficult in the critically ill. Recently, hospital beds have become available with the ability to directly weigh patients in the intensive care unit (ICU) patients directly. We sought to compare FB estimates obtained by these 2 methods in a cohort of critically ill patients. MATERIALS AND METHODS Between November 2010 and May 2011, all patients admitted in our ICU for more than 2 consecutive days and nursed on a Hill-Rom (Batesville, Ind) Total Care bed were weighed daily at midnight hours. Fluids charting was done by electronic spreadsheet with automated 24 hours calculation. Differences in BW and FB between 2 consecutive days were compared using correlation and Bland-Altman analysis. Corrections for unmeasured fluids losses were performed using a predetermined formula based on peak temperature and intubation status. RESULTS We obtained complete data in 160 (31%) of 504 admissions exceeding 2 days (153 patients) resulting in 435 data points. The change in BW over 24 hours and FB for the same period was only weakly correlated before (r = 0.34; P < .001; Fig. 1) or after correction for insensible fluid losses (r = 0.34; P < .001). On Bland-Altman plot, the mean bias was small (0.07 kg), but the 95% limits of agreement, very large (-5.8 and 6.0 kg). The lack of agreement increased with the magnitude of the changes. CONCLUSION Obtaining daily weights in ICU patients proved difficult. Compliance was poor. The correlation between changes in BWs and FB was weak. Further studies are required to establish if accurate and reproducible daily weighing of ICU patients is feasible.

Renal perfusion evaluation with contrast-enhanced ultrasonography

BACKGROUND Contrast-enhanced ultrasonography (CEUS) is a novel imaging technique that is safe and applicable on the bedside. Recent developments seem to enable CEUS to quantify organ perfusion. We performed an exploratory study to determine the ability of CEUS to detect changes in renal perfusion and to correlate them with effective renal plasma flow. METHODS CEUS with destruction-refilling sequences was studied in 10 healthy subjects, at baseline and during infusion of angiotensin II (AngII) at low (1 ng/kg/min) and high dose (3 ng/kg/min) and 1 h after oral captopril (50 mg). Perfusion index (PI) was obtained and compared with the effective renal plasma flow (ERPF) obtained by parallel para-aminohippurate (PAH) clearance. RESULTS Median PI decreased from 188.6 (baseline) to 100.4 with low-dose AngII (-47%; P < 0.02) and to 66.1 with high-dose AngII (-65%; P < 0.01) but increased to 254.7 with captopril (+35%; P > 0.2). These changes parallelled those observed with ERPF, which changed from a median of 672.1 mL/min (baseline) to 572.3 (low-dose AngII, -15%, P < 0.05) and to 427.2 (high-dose AngII, -36%, P < 0.001) and finally 697.1 (captopril, +4%, P < 0.02). CONCLUSIONS This study demonstrates that CEUS is able to detect changes in human renal cortical microcirculation as induced by AngII infusion and/or captopril administration. The changes in perfusion indices parallel those in ERPF as obtained by PAH clearance.

Hypophosphatemia in critically ill patients

PURPOSE The aim of this study was to assess the association of phosphate concentration with key clinical outcomes in a heterogeneous cohort of critically ill patients. MATERIALS AND METHODS This was a retrospective observational study at a general intensive care unit (ICU) of an Australian university teaching hospital enrolling 2730 adult critically ill patients. RESULTS We studied 10504 phosphate measurements with a mean value of 1.17 mmol/L (measurements every 28.8 hours on average). Hyperphosphatemia (inorganic phosphate [iP] concentration > 1.4 mmol/L) occurred in 45% and hypophosphatemia (iP ≤ 0.6 mmol/L) in 20%. Among patients without any episodes of hyperphosphatemia, patients with at least 1 episode of hypophosphatemia had a higher ICU mortality than those without hypophosphatemia (P = .004). In addition, ICU nonsurvivors had lower minimum phosphate concentrations than did survivors (P = .009). Similar results were seen for hospital mortality. However, on multivariable logistic regression analysis, hypophosphatemia was not independently associated with ICU mortality (adjusted odds ratio, 0.86 [95% confidence interval, 0.66-1.10]; P = .24) and hospital mortality (odds ratio, 0.89 [0.73-1.07]; P = .21). Even when different cutoff points were used for hypophosphatemia (iP ≤ 0.5, 0.4, 0.3, or 0.2 mmol/L), hypophosphatemia was not an independent risk factor for ICU and hospital morality. In addition, timing of onset and duration of hypophosphatemia were not independent risk factor for ICU and hospital mortality. CONCLUSIONS Hypophosphatemia behaves like a general marker of illness severity and not as an independent predictor of ICU or in-hospital mortality in critically ill patients.