Leah Peck

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.

Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial)☆

BACKGROUND In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. METHODS In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. RESULTS We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31). CONCLUSIONS In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment.

Bioelectrical impedance vector analysis in critically ill patients: a prospective, clinician-blinded investigation

IntroductionAssessment of fluid status in critically ill patients is challenging. We aimed to assess the feasibility and validity of bioelectrical impedance vector analysis (BIVA) as a measure of hydration in critically ill patients.MethodsWe performed twice-daily BIVA measurements and fluid balance calculations and recorded physiological variables in mechanically ventilated patients within 24 h of intensive care unit (ICU) admission for up to 5 days. Treating clinicians were blinded to BIVA results.ResultsWe performed 344 BIVA measurements in 61 patients. According to BIVA, 14 patients (23 %) were dehydrated, 22 (36 %) were normally hydrated and 25 (41 %) were overhydrated upon ICU admission. Patients with normal BIVA hydration were less sick, had fewer comorbidities and had less deranged physiology than patients found to be dehydrated or overhydrated with BIVA. Cumulative fluid balance increased in patients found to be dehydrated with BIVA by a mean of 3.4±2.2 L, whereas in patients found to be overhydrated with BIVA, it decreased by a mean of 4.5±6.9 L. In patients found to be normally hydrated with BIVA, fluid balance remained unchanged. BIVA-defined hydration increased with 1 L (median change 1.5 %, P =0.09) or 2 L (median change 0.7 %, P =0.09) of calculated fluid gains. BIVA-defined hydration decreased (median change −0.8 %, P =0.02) with a negative cumulative fluid balance of >2 L. BIVA-defined hydration between first and last measurement correlated with the corresponding change in fluid balance (ρ =0.25, P =0.05).ConclusionsBIVA is feasible in critically ill patients. Its validity is supported by the observed characteristics of patients with different degrees of BIVA hydration upon admission and by different fluid management of such patients by blinded clinicians. The sensitivity of repeated BIVA hydration measurements to detect fluid accumulation or fluid balance changes <2 L was low, however. These contradictory findings provide the rational basis for studies of BIVA-assisted fluid management in ICU patients.

Oxygen administration and monitoring for ward adult patients in a teaching hospital

Aim: The aims of this study were to describe oxygen administration and respiratory monitoring of ward patients in a tertiary teaching hospital, and to assess differences in characteristics and outcomes between patients who are receiving versus are not receiving oxygen.

High cut-off hemofiltration versus standard hemofiltration: effect on plasma cytokines.

Purpose To study the effects of continuous veno-venous hemofiltration (CVVH) with high cut-off filters (CVVH-HCO) on plasma cytokine levels, sieving coefficient and clearance compared to CVVH using standard filters (CVVH-Std) in a nested cohort within a double-blind randomized controlled trial in severe acute kidney injury (AKI) patients. Methods We measured plasma and post-filter levels of IL-6, TNF-alpha, IL-8, IL-1 beta, RANTES, IL-10, IFN-gamma and IFN-alpha in both study groups. We also measured cytokine levels in the ultrafiltrate and calculated sieving coefficients and clearances. Results By 72 hours of treatment, IL-6 had decreased during both treatments (p = 0.009 and 0.005 respectively). In contrast, IL-10 had decreased with CVVH-Std (p = 0.03) but not CVVH-HCO (p = 0.135). None of the other cytokines showed changes over time. There were also no significant between group differences in plasma levels for each cytokine over the 72-hour treatment period. For all cytokines combined, however, the median sieving coefficient was higher for CVVH-HCO (0.31 vs. 0.16; p = 0.042) as was the mass removal rate by ultrafiltration (p = 0.027). While overall combined cytokine levels had fallen to 62.2% of baseline at 72 hours for CVVH-HCO (p<0.0001) and to 75.9% of baseline with CVVH-Std (p = 0.008) there were no between group differences. Conclusions CVVH-HCO achieved greater combined sieving coefficient and mass removal rate by ultrafiltration for a group of key cytokines than CVVH-Std. However, this effect did not differentially lower their plasma level over the first 72 hours. Our study does not support the use of CVVH-HCO to lower cytokines in critically ill patients with AKI.

Neutrophil gelatinase-associated lipocalin after off pump versus on pump coronary artery surgery

Abstract Context: Cardiac surgery. Objective: To compare plasma and urinary neutrophil gelatinase-associated lipocalin (P-/U-NGAL) in on-pump (n = 43) versus off-pump (n = 40) surgery. Materials and methods: We obtained perioperative P-/U-NGAL and outcome data. Results: P-/U-NGAL increased after surgery. P-NGAL was higher post-surgery in on pump patients (139 versus 67 µg L−1; p < 0.001), but not at 24 h. There were no differences in U-NGAL. Correlation between P-/U-NGAL and plasma creatinine was weak. Discussion: P-NGAL acts like a neutrophil activation biomarker and U-NGAL like a tubular injury marker. Conclusion: On-pump patients had greater neutrophil activation. On- versus off-pump surgery had similar impact on tubular cells.

Intravenous fluid administration and monitoring for adult ward patients in a teaching hospital

Many acutely unwell, hospitalized patients receive continuous intravenous (IV) fluids. Complications of IV fluid administration include electrolyte abnormalities and fluid overload, which be detected by appropriate IV fluid administration and monitoring practices. This prospective clinical audit described the administration and monitoring of maintenance IV fluid in ward patients in an Australian tertiary teaching hospital. Of 332 inpatients (98%), 85 (26%) were receiving IV fluids. Serum electrolyte and renal function measurements were obtained in 85% versus 65% of patients receiving IV fluids versus no IV fluids (P < 0.001). Fluid balance charts were being maintained for 94% versus 44% of patients receiving IV fluids versus no IV fluids (P < 0.001). Body weight measurements were documented for 15% versus 14% for patients receiving IV fluids versus no IV fluids (P = 0.078). Findings show that approximately one-quarter of adult ward patients in our hospital received IV fluids. Monitoring of such patients using regular blood tests and fluid balance charts is high, but patient weight measurements are low. Why hospitalized patients who require maintenance IV fluids do not have regular body weight measurements requires further investigation.

Haemodynamic Impact of a Slower Pump Speed at Start of Continuous Renal Replacement Therapy in Critically Ill Adults with Acute Kidney Injury: A Prospective Before-and-After Study

Background and Objective: Patients are at risk of haemodynamic instability when starting continuous renal replacement therapy (CRRT). Methods: We compared data for ‘routine-protocol’ pump speed increases of 50 ml/min over 1–4 min with ‘slower’ increases of 20–50 ml/min over 3–10 min to achieve an operating blood flow of 200 ml/min. Results: We studied 21 routine and 20 slower CRRT starts. ‘Routine protocol’ starts reached the target pump speed more quickly than the slower CRRT start (p < 0.05). Heart rate was higher in the routine group compared to the slower group at baseline (p < 0.01) and remained so throughout. There were no significant changes in central venous pressure or mean arterial pressure, and no episodes of hypotension or hypertension, in either group, or in the subset of 17 CRRT starts in vasopressor-dependent patients. Conclusion: We cannot recommend a slower pump speed start based on our findings, but advocate for close haemodynamic monitoring, as haemodynamic changes in individual patients cannot be predicted in advance.

Neutrophil gelatinase-associated lipocalin as a marker of tubular damage appears to be unrelated to fractional excretion of sodium as a marker of tubular function in septic patients, with or without AKI

The utility of urinary biochemistry has recently been challenged [1], while there is emerging evidence that renal biomarkers may accurately quantify the risk of development of acute kidney injury (AKI) [2]. Neutrophil gelatinase-associated lipocalin (NGAL) is a marker of renal tubular damage [3]. Fractional excretion of sodium (FENa) is a marker of renal tubular function, and is a significantly cheaper investigation [4]. Insults damaging the tubules and resulting in AKI should both stimulate NGAL production and prevent resorption of sodium. Given the different pathological mechanisms underlying septic and nonseptic AKI, it is plausible that the relationship between these variables could be different in these two groups of patients [5].

High cut-off hemofiltration versus standard hemofiltration: a pilot assessment of effects on indices of apoptosis.

Objectives: To measure plasma pro-apoptotic and pro-necrotic activity in severe acute kidney injury (AKI) patients within a randomized controlled trial of continuous veno-venous hemofiltration with high cut-off filters (CVVH-HCO) versus standard filters (CVVH-Std). Methods: We measured pro-apoptotic and pro-necrotic plasma activity by trypan blue exclusion cell viability assay, detection of DNA fragmentation, and by determination of caspase-3 activity and annexin V-based apoptosis and necrosis detection assay. Results: Compared to no apoptosis or necrosis after incubation with healthy plasma, 14-18% of cells showed apoptosis and 4-8% showed necrosis after incubation with plasma from AKI patients. When comparing different measures of pro-apoptotic or pro-necrotic activity, CVVH-HCO and CVVH-Std showed no differential effects on such activity, which remained high over the first 3 days of treatment. However, using annexin V-FITC, there was a significant drop in pro-apoptotic activity across the filter for the CVVH-HCO group (p = 0.043) but not for the CVVH-Std group (p = 0.327) and a significant difference between the two groups (CVVH-HCO vs. CVVH-Std p = 0.006). Conclusions: Patients with severe AKI have increased pro-apoptotic and pro-necrotic activity. Although on single-pass effect assessment, CVVH-HCO was superior to CVVH-Std in decreasing annexin V-FITC-assessed pro-apoptotic activity, there was no overall attenuation of such activity during the first 3 days of treatment.