Tight Blood-Glucose Control without Early Parenteral Nutrition in the ICU.

BACKGROUND: Randomized, controlled trials have shown both benefit and harm from tight blood-glucose control in patients in the intensive care unit (ICU). Variation in the use of early parenteral nutrition and in insulin-induced severe hypoglycemia might explain this inconsistency. METHODS: We randomly assigned patients, on ICU admission, to liberal glucose control (insulin initiated only when the blood-glucose level was >215 mg per deciliter [>11.9 mmol per liter]) or to tight glucose control (blood-glucose level targeted with the use of the LOGIC-Insulin algorithm at 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]); parenteral nutrition was withheld in both groups for 1 week. Protocol adherence was determined according to glucose metrics. The primary outcome was the length of time that ICU care was needed, calculated on the basis of time to discharge alive from the ICU, with death accounted for as a competing risk; 90-day mortality was the safety outcome. RESULTS: Of 9230 patients who underwent randomization, 4622 were assigned to liberal glucose control and 4608 to tight glucose control. The median morning blood-glucose level was 140 mg per deciliter (interquartile range, 122 to 161) with liberal glucose control and 107 mg per deciliter (interquartile range, 98 to 117) with tight glucose control. Severe hypoglycemia occurred in 31 patients (0.7%) in the liberal-control group and 47 patients (1.0%) in the tight-control group. The length of time that ICU care was needed was similar in the two groups (hazard ratio for earlier discharge alive with tight glucose control, 1.00; 95% confidence interval, 0.96 to 1.04; P = 0.94). Mortality at 90 days was also similar (10.1% with liberal glucose control and 10.5% with tight glucose control, P = 0.51). Analyses of eight prespecified secondary outcomes suggested that the incidence of new infections, the duration of respiratory and hemodynamic support, the time to discharge alive from the hospital, and mortality in the ICU and hospital were similar in the two groups, whereas severe acute kidney injury and cholestatic liver dysfunction appeared less prevalent with tight glucose control. CONCLUSIONS: In critically ill patients who were not receiving early parenteral nutrition, tight glucose control did not affect the length of time that ICU care was needed or mortality. (Funded by the Research Foundation-Flanders and others; TGC-Fast ClinicalTrials.gov number, NCT03665207.).

Potential of Urine Biomarkers CHI3L1, NGAL, TIMP-2, IGFBP7, and Combinations as Complementary Diagnostic Tools for Acute Kidney Injury after Pediatric Cardiac Surgery: A Prospective Cohort Study.

Acute kidney injury (AKI) is common after pediatric cardiac surgery (CS). Several urine biomarkers have been validated to detect AKI earlier. The objective of this study was to evaluate urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® as predictors for AKI ≥ 1 in pediatric CS after 48 h and AKI ≥ 2 after 12 h. Pediatric patients (age < 18 year; body weight ≥ 2 kg) requiring CS were prospectively included. Urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® were measured during surgery and intensive care unit (ICU) stay and corrected for urine dilution. One hundred and one pediatric patients were included. AKI ≥ 1 within 48 h after ICU admission occurred in 62.4% and AKI ≥ 2 within 12 h in 30.7%. All damage biomarkers predicted AKI ≥ 1 within 48 h after ICU admission, when corrected for urine dilution: CHI3L1 (AUC-ROC: 0.642 (95% CI, 0.535-0.741)), NGAL (0.765 (0.664-0.848)), TIMP-2 (0.778 (0.662-0.868)), IGFBP7 (0.796 (0.682-0.883)), NephroCheck® (0.734 (0.614-0.832)). Similarly, AKI ≥ 2 within 12 h was predicted by all damage biomarkers when corrected for urine dilution: uCHI3L1 (AUC-ROC: 0.686 (95% CI, 0.580-0.780)), NGAL (0.714 (0.609-0.804)), TIMP-2 (0.830 (0.722-0.909)), IGFBP7 (0.834 (0.725-0.912)), NephroCheck® (0.774 (0.658-0.865)). After pediatric cardiac surgery, the damage biomarkers urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® reliably predict AKI after correction for urine dilution.

Video-assisted thoracic surgery in critically ill COVID-19 patients on venovenous extracorporeal membrane oxygenation.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) leads to thoracic complications requiring surgery. This is challenging, particularly in patients supported with venovenous extracorporeal membrane oxygenation (VV-ECMO) due to the need for continuous therapeutic anticoagulation. We aim to share our experience regarding the safety and perioperative management of video-assisted thoracic surgery for this specific population. METHODS: Retrospective, single-center study between November 2020 and January 2022 at the ICU department of a 1.061-bed tertiary care and VV-ECMO referral center during the COVID-19 pandemic. RESULTS: 48 COVID-19 patients were supported with VV-ECMO. A total of 14 video-assisted thoracic surgery (VATS) procedures were performed in seven patients. Indications were mostly hemothorax (85.7%). In eight procedures heparin was stopped at least 1 h before incision. A total of 10 circuit changes due to clot formation or oxygen transfer failure were required in six patients (85.7%). One circuit replacement seemed related to the preceding VATS procedure, although polytransfusion might be a contributing factor. None of the mechanical complications was fatal. Four VATS-patients (57.1%) died, of which two (50%) immediately perioperatively due to uncontrollable bleeding. All three survivors were treated with additional transarterial embolization. CONCLUSION: (1) Thoracic complications in COVID-19 patients on VV-ECMO are common. (2) Indication for VATS is mostly hemothorax (3) Perioperative mortality is high, mostly due to uncontrollable bleeding. (4) Preoperative withdrawal of anticoagulation is not directly related to a higher rate of ECMO circuit-related complications, but a prolonged duration of VV-ECMO support and polytransfusion might be. (5) Additional transarterial embolization to control postoperative bleeding may further improve outcomes.

Impact of mean perfusion pressure and vasoactive drugs on occurrence and reversal of cardiac surgery-associate acute kidney injury: A cohort study.

PURPOSE: Low cardiac output and kidney congestion are associated with acute kidney injury after cardiac surgery (CSA-AKI). This study investigates hemodynamics on CSA-AKI development and reversal. MATERIALS AND METHODS: Adult patients undergoing cardiac surgery were retrospectively included. Hemodynamic support was quantified using a new time-weighted vaso-inotropic score (VISAUC), and hemodynamic variables expressed by mean perfusion pressure and its components. The primary outcome was AKI stage ≥2 (CSA-AKI ≥2) and secondary outcome full AKI reversal before ICU discharge. RESULTS: 3415 patients were included. CSA-AKI ≥2 occurred in 37.4%. Mean perfusion pressure (MPP) (OR 0.95,95%CI 0.94-0.96, p < 0.001); and central venous pressure (CVP) (OR 1.17, 95%CI 1.13-1.22, p < 0.001) are associated with CSA-AKI ≥2 development, while VISAUC/h was not (p = 0.104). Out of 1085 CSA-AKI ≥2 patients not requiring kidney replacement therapy, 76.3% fully recovered of AKI. Full CSA-AKI reversal was associated with MPP (OR 1.02 per mmHg (95%CI 1.01-1.03, p = 0.003), and MAP (OR = 1.01 per mmHg (95%CI 1.00-1.02), p = 0.047), but not with VISAUC/h (p = 0.461). CONCLUSION: Development and full recovery of CSA-AKI ≥2 are affected by mean perfusion pressure, independent of vaso-inotropic use. CVP had a significant effect on AKI development, while MAP on full AKI reversal.

Suboptimal Beta-Lactam Therapy in Critically Ill Children: Risk Factors and Outcome.

OBJECTIVES: In critically ill children, severely altered pharmacokinetics may result in subtherapeutic ß-lactam antibiotic concentrations when standard pediatric dosing regimens are applied. However, it remains unclear how to recognize patients most at risk for suboptimal exposure and their outcome. This study aimed to: 1) describe target attainment for ß-lactam antibiotics in critically ill children, 2) identify risk factors for suboptimal exposure, and 3) study the association between target nonattainment and clinical outcome. DESIGN: Post hoc analysis of the "Antibiotic Dosing in Pediatric Intensive Care" study (NCT02456974, 2012-2019). Steady-state trough plasma concentrations were classified as therapeutic if greater than or equal to the minimum inhibitory concentration of the (suspected) pathogen. Factors associated with subtherapeutic concentrations and clinical outcome were identified by logistic regression analysis. SETTING: The pediatric and cardiac surgery ICU of a Belgian tertiary-care hospital. PATIENTS: One hundred fifty-seven patients (aged 1 mo to 15 yr) treated intravenously with amoxicillin-clavulanic acid, piperacillin-tazobactam, or meropenem. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three hundred eighty-two trough concentrations were obtained from 157 patients (median age, 1.25 yr; interquartile range, 0.4-4.2 yr). Subtherapeutic concentrations were measured in 39 of 60 (65%), 43 of 48 (90%), and 35 of 49 (71%) of patients treated with amoxicillin-clavulanic acid, piperacillin-tazobactam, and meropenem, respectively. Estimates of glomerular filtration rate (eGFR; 54% increase in odds for each sd increase in value, 95% CI, 0.287-0.736; p = 0.001) and the absence of vasopressor treatment (2.8-fold greater odds, 95% CI, 1.079-7.253; p = 0.034) were independently associated with target nonattainment. We failed to identify an association between antibiotic concentrations and clinical failure. CONCLUSIONS: Subtherapeutic ß-lactam concentrations are common in critically ill children and correlate with renal function. eGFR equations may be helpful in identifying patients who may require higher dosing. Future studies should focus on the impact of subtherapeutic concentrations on clinical outcome.

Prediction of cardiac surgery associated - acute kidney injury (CSA-AKI) by healthcare professionals and urine cell cycle arrest AKI biomarkers [TIMP-2]*[IGFBP7]: A single center prospective study (the PREDICTAKI trial).

PURPOSE: Cardiac surgery associated acute kidney injury (CSA-AKI) is a contributor to adverse outcomes. Preventive measures reduce AKI incidence in high risk patients, identified by biomarkers [TIMP-2]*[IGFBP7] (Nephrocheck®). This study investigate clinical AKI risk assessment by healthcare professionals and the added value of the biomarker result. MATERIALS AND METHODS: Adult patients were prospectively included. Healthcare professionals predicted CSA-AKI, with and without biomarker result knowledge. Predicted outcomes were AKI based on creatinine, AKI stage 3 on urine output, anuria and use of kidney replacement therapy (KRT). RESULTS: One-hundred patients were included. Consultant and ICU residents were best in AKI prediction, respectively AUROC 0.769 (95% CI, 0.672-0.850) and 0.702 (95% CI, 0.599-0.791). AUROC of NephroCheck® was 0.541 (95% CI, 0.438-0.642). AKI 3 occurred in only 4 patients; there was no anuria or use of KRT. ICU nurses and ICU residents had an AUROC for prediction of AKI 3 of respectively 0.867 (95% CI, 0.780-0.929) and 0.809 (95% CI, 0.716-0.883); for NephroCheck® this was 0.838 (95% CI, 0.750-0.904). CONCLUSIONS: Healthcare professionals performed poor or fair in predicting CSA-AKI and knowledge of Nephrocheck® result did not improved prediction. No conclusions could be made for prediction of severe AKI, due to limited number of events.

A recurrent and transesophageal echocardiography-associated outbreak of extended-spectrum ß-lactamase-producing Enterobacter cloacae complex in cardiac surgery patients.

Background: We report a recurrent outbreak of postoperative infections with extended-spectrum ß-lactamase (ESBL)-producing E. cloacae complex in cardiac surgery patients, describe the outbreak investigation and highlight the infection control measures. Methods: Cases were defined as cardiac surgery patients in Ghent University Hospital who were not known preoperatively to carry ESBL-producing E. cloacae complex and who postoperatively had a positive culture for this multiresistant organism between May 2017 and January 2018. An epidemiological investigation, including a case-control study, and environmental investigation were conducted to identify the source of the outbreak. Clonal relatedness of ESBL-producing E. cloacae complex isolates collected from case patients was assessed using whole-genome sequencing-based studies. Results: Three separate outbreak episodes occurred over the course of 9 months. A total of 8, 4 and 6 patients met the case definition, respectively. All but one patients developed a clinical infection with ESBL-producing E. cloacae complex, most typically postoperative pneumonia. Overall mortality was 22% (4/18). Environmental cultures were negative, but epidemiological investigation pointed to transesophageal echocardiography (TEE) as the outbreak source. Of note, four TEE probes showed a similar pattern of damage, which very likely impeded adequate disinfection. The first and second outbreak episode were caused by the same clone, whereas a different strain was responsible for the third episode. Conclusions: Health professionals caring for cardiac surgery patients and infection control specialists should be aware of TEE as possible infection source. Caution must be exercised to prevent and detect damage of TEE probes.

Diagnosis of cardiac surgery-associated acute kidney injury: differential roles of creatinine, chitinase 3-like protein 1 and neutrophil gelatinase-associated lipocalin: a prospective cohort study.

BACKGROUND: A common and serious complication of cardiac surgery prompting early detection and intervention is cardiac surgery-associated acute kidney injury (CSA-AKI). Urinary chitinase 3-like protein 1 (UCHI3L1) was found to predict AKI associated with critical illness in adults. Our aims were therefore to evaluate whether UCHI3L1 can also be used to predict AKI associated with elective cardiac surgery in adults, and to compare this predictive ability with that of urinary neutrophil gelatinase-associated lipocalin (UNGAL), more frequently assessed early serum creatinine (SCr) measurements, and various two-biomarker panels. METHODS: This was a single-centre prospective cohort study at the eight-bed cardiac surgery ICU of Ghent University Hospital. AKI was diagnosed and classified according to the Kidney Disease|Improving Global Outcomes definitions for the diagnosis and staging of AKI, which are based on SCr and urine output (UO). Of the 211 enrolled elective cardiac surgery patients, we included 203 patients who had no AKI pre-operatively and at time of post-operative ICU admission (t1) in the primary endpoint analysis (i.e. AKI stage ≥1 within 48 h after t1), while 210 patients without AKI stage ≥2 pre-operatively and at t1 were included in the secondary endpoint analysis (i.e. AKI stage ≥2 within 12 h after t1). Systemic and/or urine concentrations of Cr, CHI3L1 and NGAL were measured more frequently than SCr in routine early post-operative ICU practice. UO was monitored hourly in the ICU. RESULTS: Within 48 h after t1, 46.8% of the patients had developed AKI (70.5% stage 1, 20.0% stage 2 and 9.5% stage 3). In the early post-operative period, only SCr was a good predictor of AKI within 48 h after t1 (primary endpoint). SCHI3L1 combined with either UCHI3L1 or UNGAL was a good predictor of AKI stage ≥2 within 12 h after t1 (secondary endpoint). However, SCr and its absolute difference from pre-operative to early measures after surgery outperformed these combinations. CONCLUSIONS: We found that more frequent assessment of the functional biomarker SCr in the early post-operative ICU period (first 4 h) after elective cardiac surgery in adult patients had good to excellent predictive value for CSA-AKI, indicating that routine SCr assessment must become more frequent in order to detect AKI more early. This performance was in contrast with the inadequate predictive value of the urinary renal stress or damage biomarkers UCHI3L1 and UNGAL.

Impact of vancomycin protein binding on target attainment in critically ill children: back to the drawing board?

Objectives: The objectives of this observational study were to investigate plasma protein binding and to evaluate target attainment rates of vancomycin therapy in critically ill children. Patients and methods: Paediatric ICU patients, in whom intravenous intermittent dosing (ID) or continuous dosing (CD) with vancomycin was indicated, were included. Covariates on unbound vancomycin fraction and concentration were tested using a linear mixed model analysis and attainment of currently used pharmacokinetic/pharmacodynamic (PK/PD) targets was evaluated. Clinicaltrials.gov: NCT02456974. Results: One hundred and eighty-eight plasma samples were collected from 32 patients. The unbound vancomycin fraction (median = 71.1%; IQR = 65.4%-79.7%) was highly variable within and between patients and significantly correlated with total protein and albumin concentration, which were both decreased in our population. Total trough concentration (ID) and total concentration (CD) were within the aimed target concentrations in 8% of patients. The targets of AUC/MIC ≥400 and f AUC/MIC ≥200 were achieved in 54% and 83% of patients, respectively. Unbound vancomycin concentrations were adequately predicted using the following equation: unbound vancomycin concentration (mg/L) = 5.38 + [0.71 × total vancomycin concentration (mg/L)] - [0.085 × total protein concentration (g/L)]. This final model was externally validated using 51 samples from another six patients. Conclusions: The protein binding of vancomycin in our paediatric population was lower than reported in non-critically ill adults and exhibited large variability. Higher target attainment rates were achieved when using PK/PD indices based on unbound concentrations, when compared with total concentrations. These results highlight the need for protein binding assessment in future vancomycin PK/PD research.

Acute Kidney Injury in Cardiorenal Syndrome Type 1 Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: We evaluated the epidemiology and outcome of acute kidney injury (AKI) in patients with cardiorenal syndrome type 1 (CRS-1) and its subgroups: acute heart failure (AHF), acute coronary syndrome (ACS) and after cardiac surgery (CS). SUMMARY: We performed a systematic review and meta-analysis. CRS-1 was defined by AKI (based on RIFLE, AKIN and KDIGO), worsening renal failure (WRF) and renal replacement therapy (RRT). We investigated the three most common clinical causes of CRS-1: AHF, ACS and CS. Out of 332 potential papers, 64 were eligible - with AKI used in 41 studies, WRF in 25 and RRT in 20. The occurrence rate of CRS-1, defined by AKI, WRF and RRT, was 25.4, 22.4 and 2.6%, respectively. AHF patients had a higher occurrence rate of CRS-1 compared to ACS and CS patients (AKI: 47.4 vs. 14.9 vs. 22.1%), but RRT was evenly distributed among the types of acute cardiac disease. AKI was associated with an increased mortality rate (risk ratio = 5.14, 95% CI 3.81-6.94; 24 studies and 35,227 patients), a longer length of stay in the intensive care unit [LOSICU] (median duration = 1.37 days, 95% CI 0.41-2.33; 9 studies and 10,758 patients) and a longer LOS in hospital [LOShosp] (median duration = 3.94 days, 95% CI 1.74-6.15; 8 studies and 35,227 patients). Increasing AKI severity was associated with worse outcomes. The impact of CRS-1 defined by AKI on mortality was greatest in CS patients. RRT had an even greater impact compared to AKI (mortality risk ratio = 9.2, median duration of LOSICU = 10.6 days and that of LOShosp = 20.2 days). KEY MESSAGES: Of all included patients, almost one quarter developed AKI and approximately 3% needed RRT. AHF patients experienced the highest occurrence rate of AKI, but the impact on mortality was greatest in CS patients.

Acute and critically ill peripartum cardiomyopathy and 'bridge to' therapeutic options: a single center experience with intra-aortic balloon pump, extra corporeal membrane oxygenation and continuous-flow left ventricular assist devices.

INTRODUCTION: Peripartum cardiomyopathy (PPCM) patients refractory to medical therapy and intra-aortic balloon pump (IABP) counterpulsation or in whom weaning from these therapies is impossible, are candidates for a left ventricular assist device (LVAD) as a bridge to recovery or transplant. Continuous-flow LVADs are smaller, have a better long-term durability and are associated with better outcomes. Extra corporeal membrane oxygenation (ECMO) can be used as a temporary support in patients with refractory cardiogenic shock. The aim of this study was to evaluate the efficacy and safety of mechanical support in acute and critically ill PPCM patients. METHODS: This was a retrospective search of the patient database of the Ghent University hospital (2000 to 2010). RESULTS: Six PPCM-patients were treated with mechanical support. Three patients presented in the postpartum period and three patients at the end of pregnancy. All were treated with IABP, the duration of IABP support ranged from 1 to 13 days. An ECMO was inserted in one patient who presented with cardiogenic shock, multiple organ dysfunction syndrome and a stillborn baby. Two patients showed partial recovery and could be weaned off the IABP. Four patients were implanted with a continuous-flow LVAD (HeartMate II, Thoratec Inc.), including the ECMO-patient. Three LVAD patients were successfully transplanted 78, 126 and 360 days after LVAD implant; one patient is still on the transplant waiting list. We observed one peripheral thrombotic complication due to IABP and five early bleeding complications in three LVAD patients. One patient died suddenly two years after transplantation. CONCLUSIONS: In PPCM with refractory heart failure IABP was safe and efficient as a bridge to recovery or as a bridge to LVAD. ECMO provided temporary support as a bridge to LVAD, while the newer continuous-flow LVADs offered a safe bridge to transplant.

Surgical decompression for abdominal compartment syndrome after emergency cardiac surgery.

Abdominal compartment syndrome typically occurs in patients after abdominal surgical procedures or trauma. Abdominal compartment syndrome is also increasingly described in conditions not related to abdominal operations, such as fluid resuscitation or burns. We report two patients who required surgical abdominal decompression for abdominal compartment syndrome that developed early after emergency coronary artery bypass graft surgery. No intraabdominal abnormalities were found at operation. Both patients had a protracted clinical course, but they survived and were discharged from the hospital.

Polyurethane cuffed endotracheal tubes to prevent early postoperative pneumonia after cardiac surgery: a pilot study.

OBJECTIVE: Patients receiving mechanical ventilation through an endotracheal tube are at increased risk for pneumonia. Because microaspiration of contaminated supraglottic secretions past the endotracheal tube cuff is considered to be central in the pathogenesis of ventilator-associated and postoperative pneumonia, better sealing of the upper trachea by the endotracheal tube cuff could possibly reduce this risk. We therefore postulated that use of a polyurethane cuffed tube would prevent early postoperative pneumonia through this mechanism in a population of cardiac surgical patients. METHODS: In a prospective, single-blind, randomized study, patients scheduled for cardiac surgery were allocated to intubation with a polyurethane cuffed endotracheal tube or the routinely used polyvinyl chloride cuffed endotracheal tube. Patients were scheduled for routine or emergency cardiac surgery and admitted to an 8-bed cardiac surgical intensive care unit of a tertiary care hospital. RESULTS: A total of 134 patients were available for analysis (67 in each group). Whereas mortality was not different between the groups, the incidence of early postoperative pneumonia and empirical prescription of antibiotic therapy were significantly lower in the polyurethane group than in the polyvinyl chloride group (23% vs 42%, P < .03). Intensive care unit and hospital stays were not significantly different between the two study subsets (3 +/- 5 days vs 3 +/- 4 days and 16 +/- 9 vs 17+/-11 days, respectively). In a multivariate regression analysis, preoperative serum creatinine levels (odds ratio 1.85, confidence interval 1.02-3.37, P = .04) and perioperative transfusion (odds ratio 1.50, confidence interval 1.08-3.37, P = .015) were independently associated with increased risk of early postoperative pneumonia, whereas use of a polyurethane endotracheal tube was protective (odds ratio 0.31, confidence interval 0.13-0.77, P = .01). CONCLUSION: Polyurethane cuffed endotracheal tubes can reduce the frequency of early postoperative pneumonia in cardiac surgical patients.