Renin as a Marker of Tissue-Perfusion and Prognosis in Critically Ill Patients*

Renin as a Marker of Tissue-Perfusion and Prognosis in Critically Ill Patients*

by Gleeson, Patrick J.; Crippa, Ilaria Alice; Mongkolpun, Wasineenart; Cavicchi, Federica Zama; Van Meerhaeghe, Tess; Brimioulle, Serge; Taccone, Fabio Silvio; Vincent, Jean-Louis; Creteur, Jacques

Critical Care Medicine: February 2019 - Volume 47 - Issue 2 - p 152–158

Objectives: To characterize renin in critically ill patients. Renin is fundamental to circulatory homeostasis and could be a useful marker of tissue-perfusion. However, diurnal variation, continuous renal replacement therapy and drug-interference could confound its use in critical care practice.

Design: Prospective observational study. Setting: Single-center, mixed medical-surgical ICU in Europe. Patients: Patients over 18 years old with a baseline estimated glomerular filtration rate greater than 30 mL/min/1.73 m2 and anticipated ICU stay greater than 24 hours. Informed consent was obtained from the patient or next-of-kin. Interventions: Direct plasma renin was measured in samples drawn 6-hourly from arterial catheters in recumbent patients and from extracorporeal continuous renal replacement therapy circuits. Physiologic variables and use of drugs that act on the renin-angiotensin-aldosterone system were recorded prospectively. Routine lactate measurements were used for comparison.

Measurements and Main Results: One-hundred twelve arterial samples (n = 112) were drawn from 20 patients (65% male; mean ± SD, 60 ± 14 yr old) with septic shock (30%), hemorrhagic shock (15%), cardiogenic shock (20%), or no circulatory shock (35%). The ICU mortality rate was 30%. Renin correlated significantly with urine output (repeated-measures correlation coefficient = –0.29; p = 0.015) and mean arterial blood pressure (repeated-measures correlation coefficient = –0.35; p < 0.001). There was no diurnal variation of renin or significant interaction of renin-angiotensin-aldosterone system drugs with renin in this population. Continuous renal replacement therapy renin removal was negligible (mass clearance ± SD 4% ± 4.3%). There was a significant difference in the rate of change of renin over time between survivors and nonsurvivors (–32 ± 26 μU/timepoint vs +92 ± 57 μU/timepoint p = 0.03; mean ± SEM), but not for lactate (–0.14 ± 0.04 mM/timepoint vs +0.15 ± 0.21 mM/timepoint; p = 0.07). Maximum renin achieved significant prognostic value for ICU mortality (receiver operator curve area under the curve 0.80; p = 0.04), whereas maximum lactate did not (receiver operator curve area under the curve, 0.70; p = 0.17).

Conclusions: In an heterogeneous ICU population, renin measurement was not significantly affected by diurnal variation, continuous renal replacement therapy, or drugs. Renin served as a marker of tissue-perfusion and outperformed lactate as a predictor of ICU mortality.

Long-Term Effects of Phased Implementation of Antimicrobial Stewardship in Academic ICUs: 2007–2015*

Long-Term Effects of Phased Implementation of Antimicrobial Stewardship in Academic ICUs: 2007–2015*

by Morris, Andrew M.; Bai, Anthony; Burry, Lisa; Dresser, Linda D.; Ferguson, Niall D.; Lapinsky, Stephen E.; Lazar, Neil M.; McIntyre, Mark; Matelski, John; Minnema, Brian; Mok, Katie; Nelson, Sandra; Poutanen, Susan M.; Singh, Jeffrey M.; So, Miranda; Steinberg, Marilyn; Bell, Chaim M.

Critical Care Medicine: February 2019 - Volume 47 - Issue 2 - p 159–166

Objectives: Antimicrobial stewardship is advocated to reduce antimicrobial resistance in ICUs by reducing unnecessary antimicrobial consumption. Evidence has been limited to short, single-center studies. We evaluated whether antimicrobial stewardship in ICUs could reduce antimicrobial consumption and costs.

Design: We conducted a phased, multisite cohort study of a quality improvement initiative. Setting: Antimicrobial stewardship was implemented in four academic ICUs in Toronto, Canada beginning in February 2009 and ending in July 2012. Patients: All patients admitted to each ICU from January 1, 2007, to December 31, 2015, were included. Interventions: Antimicrobial stewardship was delivered using in-person coaching by pharmacists and physicians three to five times weekly, and supplemented with unit-based performance reports. Total monthly antimicrobial consumption (measured by defined daily doses/100 patient-days) and costs (Canadian dollars/100 patient-days) before and after antimicrobial stewardship implementation were measured.

Measurements and Main Results: A total of 239,123 patient-days (57,195 patients) were analyzed, with 148,832 patient-days following introduction of antimicrobial stewardship. Antibacterial use decreased from 120.90 to 110.50 defined daily dose/100 patient-days following introduction of antimicrobial stewardship (adjusted intervention effect –12.12 defined daily dose/100 patient-days; 95% CI, –16.75 to –7.49; p < 0.001) and total antifungal use decreased from 30.53 to 27.37 defined daily doses/100 patient-days (adjusted intervention effect –3.16 defined daily dose/100 patient-days; 95% CI, –8.33 to 0.04; p = 0.05). Monthly antimicrobial costs decreased from $3195.56 to $1998.59 (adjusted intervention effect –$642.35; 95% CI, –$905.85 to –$378.84; p < 0.001) and total antifungal costs were unchanged from $1771.86 to $2027.54 (adjusted intervention effect –$355.27; 95% CI, –$837.88 to $127.33; p = 0.15). Mortality remained unchanged, with no consistent effects on antimicrobial resistance and candidemia.

Conclusions: Antimicrobial stewardship in ICUs with coaching plus audit and feedback is associated with sustained improvements in antimicrobial consumption and cost. ICUs with high antimicrobial consumption or expenditure should consider implementing antimicrobial stewardship programs.

Evaluating Delivery of Low Tidal Volume Ventilation in Six ICUs Using Electronic Health Record Data*

Evaluating Delivery of Low Tidal Volume Ventilation in Six ICUs Using Electronic Health Record Data*

by Sjoding, Michael W.; Gong, Michelle N.; Haas, Carl F.; Iwashyna, Theodore J.  

Critical Care Medicine: January 2019 - Volume 47 - Issue 1 - p 56–61

Objectives: Mechanical ventilation with low tidal volumes is recommended for all patients with acute respiratory distress syndrome and may be beneficial to other intubated patients, yet consistent implementation remains difficult to obtain. Using detailed electronic health record data, we examined patterns of tidal volume administration, the effect on clinical outcomes, and alternate metrics for evaluating low tidal volume compliance in clinical practice.

Design: Observational cohort study.

Setting: Six ICUs in a single hospital system. Patients: Adult patients who received invasive mechanical ventilation more than 12 hours. Interventions: None.

Measurements and Main Results: Tidal volumes were analyzed across 1,905 hospitalizations. Although mean tidal volume was 6.8 mL/kg predicted body weight, 40% of patients were exposed to tidal volumes greater than 8 mL/kg predicted body weight, with 11% for more than 24 hours. At a patient level, exposure to 24 total hours of tidal volumes greater than 8 mL/kg predicted body weight was associated with increased mortality (odds ratio, 1.82; 95% CI, 1.20–2.78), whereas mean tidal volume exposure was not (odds ratio, 0.87/1 mL/kg increase; 95% CI, 0.74–1.02). Initial tidal volume settings strongly predicted exposure to volumes greater than 8 mL/kg for 24 hours; the adjusted rate was 21.5% when initial volumes were greater than 8 mL/kg predicted body weight and 7.1% when initial volumes were less than 8 mL/kg predicted body weight. Across ICUs, correlation of mean tidal volume with alternative measures of low tidal volume delivery ranged from 0.38 to 0.66. Conclusions: Despite low mean tidal volume in the cohort, a significant percentage of patients were exposed to a prolonged duration of high tidal volumes which was correlated with higher mortality. Detailed ventilator records in the electronic health record provide a unique window for evaluating low tidal volume delivery and targets for improvement.

Combination of High-Calorie Delivery and Organ Failure Increases Mortality Among Patients With Acute Respiratory Distress Syndrome

Combination of High-Calorie Delivery and Organ Failure Increases Mortality Among Patients With Acute Respiratory Distress Syndrome

by Peterson, Sarah J.; McKeever, Liam; Lateef, Omar B.; Freels, Sally; Fantuzzi, Giamila; Braunschweig, Carol A.  

Critical Care Medicine: January 2019 - Volume 47 - Issue 1 - p 69–75

Objectives: Among critically ill patients, the benefits of nutrition support may vary depending on severity of organ dysfunction. The objective of the current article was to explore the relationship between organ failure and calories exposure with hospital mortality during the first week of acute respiratory distress syndrome.

Design: Retrospective observational study.

Setting: Single-center ICU. Patients: Adults admitted to the ICU with a diagnosis of acute respiratory distress syndrome. Interventions: Calorie delivery from enteral nutrition, parenteral nutrition, propofol, and dextrose containing fluids were collected for 7 days following intubation. Sequential Organ Failure Assessment score was calculated at ICU admit and for the same 7 days to describe organ dysfunction; four different Sequential Organ Failure Assessment variables were created 1) Sequential Organ Failure Assessment at ICU admit, 2) average Sequential Organ Failure Assessment for the first 7 days following intubation, 3) the highest Sequential Organ Failure Assessment for the first 7 days following intubation, and 4) change in Sequential Organ Failure Assessment from intubation to 7 days later.

Measurements and Main Results: A total of 298 patients were included. Sequential Organ Failure Assessment at ICU admit, average Sequential Organ Failure Assessment for the first 7 days following intubation, highest Sequential Organ Failure Assessment for the first 7 days following intubation, change in Sequential Organ Failure Assessment from intubation to 7 days later, and calorie delivery the first 7 days following intubation were all associated with increased likelihood of mortality. Compared with patients with low organ failure and low-calorie delivery, those with high-calorie delivery and low organ failure, low-calorie delivery and high organ failure, and the combination of both high organ failure with high-calorie delivery were associated with an incremental increase in the likelihood or mortality.

Conclusions: Organ failure appears to modify the relationship between calorie exposure and ICU outcome. Additional research is needed to identify appropriate thresholds for safe calorie exposure with increased organ failure.

Female Physician Leadership During Cardiopulmonary Resuscitation Is Associated With Improved Patient Outcomes*

Female Physician Leadership During Cardiopulmonary Resuscitation Is Associated With Improved Patient Outcomes*

by Meier, Angela; Yang, Jenny; Liu, Jinyuan; Beitler, Jeremy R.; Tu, Xin M.; Owens, Robert L.; Sundararajan, Radhika L.; Malhotra, Atul; Sell, Rebecca E.  

Critical Care Medicine: January 2019 - Volume 47 - Issue 1 - p e8–e13

Objectives: A recently published simulation study suggested that women are inferior leaders of cardiopulmonary resuscitation efforts. The aim of this study was to compare female and male code leaders in regard to cardiopulmonary resuscitation outcomes in a real-world clinical setting.

Design: Retrospective cohort review. Setting: Two academic, urban hospitals in San Diego, California. Subjects: One-thousand eighty-two adult inpatients who suffered cardiac arrest and underwent cardiopulmonary resuscitation. Interventions: None.

Measurements and Main Results: We analyzed whether physician code leader gender was independently associated with sustained return of spontaneous circulation and survival to discharge and with markers of quality cardiopulmonary resuscitation. Of all arrests, 327 (30.1%) were run by female physician code leaders with 251 (76.8%) obtaining return of spontaneous circulation, and 122 (37.3%) surviving to discharge. Male physicians ran 757 codes obtaining return of spontaneous circulation in 543 (71.7%) with 226 (29.9%) surviving to discharge. When adjusting for variables, female physician code leader gender was independently associated with a higher likelihood of return of spontaneous circulation (odds ratio, 1.36; 95% CI, 1.01–1.85; p = 0.049) and survival to discharge (odds ratio, 1.53; 95% CI, 1.15–2.02; p < 0.01). Additionally, the odds ratio for survival to discharge was 1.62 (95% CI, 1.13–2.34; p < 0.01) for female physicians with a female code nurse when compared with male physician code leaders paired with a female code nurse. Gender of code leader was not associated with cardiopulmonary resuscitation quality.

Conclusions: In contrast to data derived from a simulated setting with medical students, real life female physician leadership of cardiopulmonary resuscitation is not associated with inferior outcomes. Appropriately, trained physicians can lead high-quality cardiopulmonary resuscitation irrespective of gender.

Reassessment of the Accuracy of Cardiac Doppler Pulmonary Artery Pressure Measurements in Ventilated ICU Patients: A Simultaneous Doppler-Catheterization Study*

Reassessment of the Accuracy of Cardiac Doppler Pulmonary Artery Pressure Measurements in Ventilated ICU Patients: A Simultaneous Doppler-Catheterization Study*

by Mercado, Pablo; Maizel, Julien; Beyls, Christophe; Kontar, Loay; Orde, Sam; Huang, Stephen; McLean, Anthony; Tribouilloy, Christophe; Slama, Michel  

Critical Care Medicine: January 2019 - Volume 47 - Issue 1 - p 41–48

Objectives: Doppler echocardiography is a well-recognized technique for the noninvasive evaluation of pulmonary artery pressure; however, little information is available concerning patients receiving mechanical ventilation. Furthermore, recent studies have debatable results regarding the relevance of this technique to assess pulmonary artery pressure. The aim of our study was to reassess the accuracy of Doppler echocardiography to evaluate pulmonary artery pressure and to predict pulmonary hypertension.

Design: Prospective observational study. Setting: Amiens ICU, France. Patients. ICU patients receiving mechanical ventilation. Interventions: In 40 patients, we simultaneously recorded Doppler echocardiography variables (including tricuspid regurgitation and pulmonary regurgitation) and invasive central venous pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, and mean pulmonary artery pressure.

Measurements and Main Results: Systolic pulmonary artery pressure assessed from the tricuspid regurgitation derived maximal pressure gradient added to the central venous pressure demonstrated the best correlation with the invasive systolic pulmonary artery pressure (r = 0.87) with a small bias (–3 mm Hg) and a precision of 9 mm Hg. A Doppler echocardiography systolic pulmonary artery pressure greater than 39 mm Hg predicted pulmonary hypertension (mean pulmonary artery pressure ≥ 25 mm Hg) with 100% sensitivity and specificity. Tricuspid regurgitation maximal velocity greater than 2.82 m/s as well as tricuspid regurgitation pressure gradient greater than 32 mm Hg predicted the presence of pulmonary hypertension. Pulmonary regurgitation was recorded in 10 patients (25%). No correlation was found between pulmonary regurgitation velocities and either mean pulmonary artery pressure or diastolic pulmonary artery pressure. Pulmonary acceleration time less than 57 ms and isovolumic relaxation time less than 40 ms respectively predicted pulmonary hypertension 100% of the time and had a 100% negative predictive value. Conclusions: Tricuspid regurgitation maximal velocity pressure gradient added to invasive central venous pressure accurately estimates systolic pulmonary artery pressure and mean pulmonary artery pressure in ICU patients receiving mechanical ventilation and may predict pulmonary hypertension.

Minimal Impact of Implemented Early Warning Score and Best Practice Alert for Patient Deterioration*

Minimal Impact of Implemented Early Warning Score and Best Practice Alert for Patient Deterioration*

by Bedoya, Armando D.; Clement, Meredith E.; Phelan, Matthew; Steorts, Rebecca C.; O’Brien, Cara; Goldstein, Benjamin A.  

Critical Care Medicine: January 2019 - Volume 47 - Issue 1 - p 49–55

Objectives: Previous studies have looked at National Early Warning Score performance in predicting in-hospital deterioration and death, but data are lacking with respect to patient outcomes following implementation of National Early Warning Score. We sought to determine the effectiveness of National Early Warning Score implementation on predicting and preventing patient deterioration in a clinical setting.

Design: Retrospective cohort study. Setting: Tertiary care academic facility and a community hospital. Patients: Patients 18 years old or older hospitalized from March 1, 2014, to February 28, 2015, during preimplementation of National Early Warning Score to August 1, 2015, to July 31, 2016, after National Early Warning Score was implemented. Interventions: Implementation of National Early Warning Score within the electronic health record and associated best practice alert.

Measurements and Main Results: In this study of 85,322 patients (42,402 patients pre-National Early Warning Score and 42,920 patients post-National Early Warning Score implementation), the primary outcome of rate of ICU transfer or death did not change after National Early Warning Score implementation, with adjusted hazard ratio of 0.94 (0.84–1.05) and 0.90 (0.77–1.05) at our academic and community hospital, respectively. In total, 175,357 best practice advisories fired during the study period, with the best practice advisory performing better at the community hospital than the academic at predicting an event within 12 hours 7.4% versus 2.2% of the time, respectively. Retraining National Early Warning Score with newly generated hospital-specific coefficients improved model performance.

Conclusions: At both our academic and community hospital, National Early Warning Score had poor performance characteristics and was generally ignored by frontline nursing staff. As a result, National Early Warning Score implementation had no appreciable impact on defined clinical outcomes. Refitting of the model using site-specific data improved performance and supports validating predictive models on local data.

Above the GRADE: Evaluation of Guidelines in Critical Care Medicine*

Above the GRADE: Evaluation of Guidelines in Critical Care Medicine*

by Sims, Charles R.; Warner, Matthew A.; Stelfox, Henry Thomas; Hyder, Joseph A.  

Critical Care Medicine: January 2019 - Volume 47 - Issue 1 - p 109–113

Objectives: We examined recommendations within critical care guidelines to describe the pairing patterns for strength of recommendation and quality of evidence. We further identified recommendations where the reported strength of recommendation was strong while the reported quality of evidence was not high/moderate and then assessed whether such pairings were within five paradigmatic situations offered by Grading of Recommendations Assessment, Development and Evaluation methodology to justify such pairings.

Data Sources and Extraction: We identified all clinical critical care guidelines published online from 2011 to 2017 by the Society of Critical Care Medicine along with individual guidelines published by Surviving Sepsis Campaign, Kidney Disease Improving Global Outcomes, American Society for Parenteral and Enteral Nutrition, and the Infectious Disease Society of America/American Thoracic Society.

Data Synthesis: In all, 15 documents specifying 681 eligible recommendations demonstrated variation in strength of recommendation (strong n = 215 [31.6%], weak n = 345 [50.7%], none n = 121 [17.8%]) and in quality of evidence (high n = 41 [6.0%], moderate n = 151 [22.2%], low/very low n = 298 [43.8%], and Expert Consensus/none n = 191 [28.1%]). Strength of recommendation and quality of evidence were positively correlated (ρ = 0.66; p < 0.0001). Of 215 strong recommendations, 69 (32.1%) were discordantly paired with evidence other than high/moderate. Twenty-two of 69 (31.9%) involved Strong/Expert Consensus recommendations, a category discouraged by Grading of Recommendations Assessment, Development and Evaluation methodology. Forty-seven of 69 recommendations (68.1%) were comprised of Strong/Low or Strong/Very Low variation requiring justification within five paradigmatic scenarios. Among distribution in the five paradigmatic scenarios of Strong/Low and Strong/Very Low recommendations, the most common paradigmatic scenario was life threatening situation (n = 20/47; 42.6%). Four Strong/Low or Strong/Very Low recommendations (4/47; 8.5%) were outside Grading of Recommendations Assessment, Development and Evaluation methodology.

Conclusions: Among a large, diverse assembly of critical care guideline recommendations using Grading of Recommendations Assessment, Development and Evaluation methodology, the strength of evidence of a recommendation was generally associated with the quality of evidence. However, strong recommendations were not infrequently made in the absence of high/moderate quality of evidence. To improve clarity and uptake, future guideline statements may specify why such pairings were made, avoid such pairings when outside of Grading of Recommendations Assessment, Development and Evaluation criteria, and consider separate language for Expert Consensus recommendations (good practice statements).

Renal Outcomes of Vasopressin and Its Analogs in Distributive Shock: A Systematic Review and Meta-Analysis of Randomized Trials

Renal Outcomes of Vasopressin and Its Analogs in Distributive Shock: A Systematic Review and Meta-Analysis of Randomized Trials

by Nedel, Wagner L.; Rech, Tatiana H.; Ribeiro, Rodrigo A.; Pellegrini, José Augusto S.; Moraes, Rafael B.  

Critical Care Medicine: January 2019 - Volume 47 - Issue 1 - p e44–e51

Objectives: To systematically review the literature and synthesize evidence concerning the effects of vasopressin and its analogs compared with other vasopressors in distributive shock, focusing on renal outcomes. Data Sources: We performed a systematic review in MEDLINE, Embase, Cochrane Central, and Clinicaltrials.gov databases.

Study Selection: Randomized clinical trials that compared vasopressin and its analogs with other vasopressors and reported renal outcomes in adult patients with distributive shock.

Data Extraction: Paired reviewers independently screened citations, conducted data extraction and assessed risk of bias. Three prespecified subgroup analyses were conducted. Three main outcomes related to acute renal failure were analyzed: the need for renal replacement therapy, acute kidney injury incidence, and acute kidney injury-free days. I2 test was used to evaluate heterogeneity between studies. Substantial heterogeneity was defined as I2 greater than 50%. A random-effects model with Mantel-Haenszel weighting was used for all analyses. Heterogeneity was explored using subgroup analysis. The quality of evidence for intervention effects was summarized using Grading of Recommendations Assessment, Development, and Evaluation methodology. This study was registered in the PROSPERO database (CRD42017054324).

Data Synthesis: Three-thousand twenty-six potentially relevant studies were identified, and 30 articles were reviewed in full. Seventeen studies met the inclusion criteria, including a total of 2,833 individuals. Of these, 11 studies (2,691 individuals) were suitable for quantitative meta-analysis. Overall, the evidence was of low to moderate quality. Patients who received vasopressin and its analogs had a reduced need for renal replacement therapy (odds ratio, 0.59 [0.37–0.92]; p = 0.02; I2 = 49%) and a lower acute kidney injury incidence (odds ratio, 0.58 [0.37–0.92]; p = 0.02; I2 = 63%). These results should be interpreted with caution, due to excessive heterogeneity. Acute kidney injury-free data was not pooled, since the small number of studies and extreme heterogeneity. Conclusions: In patients with distributive shock, vasopressin and its analogs use is associated with a reduced need for renal replacement therapy and lower acute kidney injury incidence. These results are supported by high risk of bias evidence.