Critical Care Initiation Research Articles

Validation of a pre-established triage protocol for critically ill patients in a COVID-19 outbreak under resource scarcity: A retrospective multicenter cohort study.

In case of COVID-19 related scarcity of critical care resources, an early French triage algorithm categorized critically ill patients by probability of survival based on medical history and severity, with four priority levels for initiation or continuation of critical care: P1 -high priority, P2 -intermediate priority, P3 -not needed, P4 -not appropriate. This retrospective multi-center study aimed to assess its classification performance and its ability to help saving lives under capacity saturation. ICU patients admitted for severe COVID-19 without triage in spring 2020 were retrospectively included from three hospitals. Demographic data, medical history and severity items were collected. Priority levels were retrospectively allocated at ICU admission and on ICU day 7-10. Mortality rate, cumulative incidence of death and of alive ICU discharge, length of ICU stay and of mechanical ventilation were compared between priority levels. Calculated mortality and survival were compared between full simulated triage and no triage. 225 patients were included, aged 63.1±11.9 years. Median SAPS2 was 40 (IQR 29-49). At the end of follow-up, 61 (27%) had died, 26 were still in ICU, and 138 had been discharged. Following retrospective initial priority allocation, mortality rate was 53% among P4 patients (95CI 34-72%) versus 23% among all P1 to P3 patients (95CI 17-30%, chi-squared p = 5.2e-4). The cumulative incidence of death consistently increased in the order P3, P1, P2 and P4 both at admission (Gray's test p = 3.1e-5) and at reassessment (p = 8e-5), and conversely for that of alive ICU discharge. Reassessment strengthened consistency. Simulation under saturation showed that this two-step triage protocol could have saved 28 to 40 more lives than no triage. Although it cannot eliminate potentially avoidable deaths, this triage protocol proved able to adequately prioritize critical care for patients with highest probability of survival, hence to save more lives if applied.

Ebola outbreak in Guinea, 2021: Clinical care of patients with Ebola virus disease.

Experience from the Zaire Ebolavirus epidemic in the eastern Democratic Republic of the Congo (2018-2020) demonstrates that early initiation of essential critical care and administration of Zaire Ebolavirus specific monoclonal antibodies may be associated with improved outcomes among patients with Ebola virus disease (EVD). This series describes 13 EVD patients and 276 patients with suspected EVD treated during a Zaire Ebolavirus outbreak in Guinea in 2021. Patients with confirmed or suspected EVD were treated in two Ebola treatment centres (ETC) in the region of N'zérékoré. Data were reviewed from all patients with suspected or confirmed EVD hospitalised in these two ETCs during the outbreak (14 February 2021 - 19 June 2021). Ebola-specific monoclonal antibodies, were available 2 weeks after onset of the outbreak. Nine of the 13 EVD patients (age range: 22-70 years) survived. The four EVD patients who died, including one pregnant woman, presented with multi-organ dysfunction and died within 48 h of admission. All eight patients who received Ebola-specific monoclonal antibodies survived. Four of the 13 EVD patients were health workers. Improvement of ETC design facilitated implementation of WHO-recommended 'optimized supportive care for EVD'. In this context, pragmatic clinical training was integrated in routine ETC activities. Initial clinical manifestations of 13 confirmed EVD patients were similar to those of 276 patients with suspected, but subsequently non confirmed EVD. These patients suffered from other acute infections (e.g. malaria in 183 of 276 patients; 66%). Five of the 276 patients with suspected EVD died. One of these five patients had Lassa virus disease and a coronavirus disease 2019 (COVID-19) co-infection. Multidisciplinary outbreak response teams can rapidly optimise ETC design. Trained clinical teams can provide WHO-recommended optimised supportive care, including safe administration of Ebola-specific monoclonal antibodies. Pragmatic training in essential critical care can be integrated in routine ETC activities. This article describes clinical realities associated with implementation of WHO-recommended standards of 'optimized supportive care' and administration of Ebola virus specific treatments. In this context, the importance of essential design principles of ETCs is underlined, which allow continuous visual contact and verbal interaction of health workers and families with their patients. Elements that may contribute to further quality of care improvements for patients with confirmed or suspected EVD are discussed.

EAR PIERCING: A GATEWAY TO TETANUS

Tetanus is initiated by the release of neurotoxins. The progressive paralysis of several muscles is due to contamination of the wound by the toxin. The case under discussion was about a patient with the tetanus infection after ear piercing due to unsterilized instruments and lack of awareness of complications. Due to the late presentation to the hospital, leading to a delay in treatment, the child could not survive. Physicians need to have a vigilant eye to have a high suspicion for tetanus at a very early stage and immediate initiation of advanced critical care, which can favour lifesaving interventions. Prophylactic tetanus toxoid should be administered before any body piercing

A CASE OF VASOSPASTIC ANGINA: A DIAGNOSTIC DILEMMA

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Coronary artery spasm is characterized by episodic angina typically occurring at rest with transient ST-segment elevation on electrocardiogram (EKG). This syndrome occurs as a brief and unexpected narrowing of one of the coronary arteries. CASE PRESENTATION: We present a 60-year-old man with acute onset of typical chest pain. He has a history of coronary artery disease status post bypass surgery with left internal mammary artery (LIMA) to the left anterior descending artery (LAD), coronary artery spasm, and a 40-pack-year smoking history. In the Emergency Department, he developed a second episode of squeezing chest pain with left arm numbness resolving spontaneously. Initial EKG demonstrated minimal anterior lead ST-segment elevation with elevated high sensitivity troponin I of 30 ng/L. Cardiovascular exam was unremarkable. He was admitted with concerns for acute coronary syndrome and over the course of his hospitalization he developed a recurrent episode of acute chest pain with dyspnea. His EKG revealed sinus bradycardia with ST-segment elevation in leads II, III, and aVF, thus prompting transfer to the critical care unit and initiation of nitroglycerin drip and a heparin infusion. A repeat EKG nine minutes later showed resolution of ST-segment elevation. The patient underwent diagnostic angiography, results including patency of LIMA to LAD and a 99% occlusion of the right coronary artery (RCA). Intracoronary nitroglycerin provided complete relief of symptoms and a now normal appearing RCA with no evidence for occlusive disease. A diagnosis of vasospastic angina was made and the patient was started on amlodipine along with isosorbide mononitrate. DISCUSSION: The diagnosis of coronary spasm may be overlooked as its presentation mimics an acute myocardial infarction. Improvement of symptoms with EKG resolution following the administration of nitroglycerin is suggestive of vasospasm. CONCLUSIONS: Cigarette smoking remains a major risk factor for vasospastic angina and cessation should be the mainstay treatment. Medical management includes calcium channel blockers as first-line and nitrates as second-line therapy. Reference #1: Tandon V, Mosebach CM, Kumar M, Joshi S. Refractory Vasospastic Angina: When Typical Medications Don't Work. Cureus. 2019;11(2):e4134. Published 2019 Feb 25. doi:10.7759/cureus.4134 Reference #2: Davies O, Ajayeoba O, Kurian D. Coronary artery spasm: An often overlooked diagnosis. Niger Med J. 2014;55(4):356–358. doi:10.4103/0300-1652.137231 DISCLOSURES: No relevant relationships by Jessica Boldridge, source=Web Response No relevant relationships by Steve Isserman, source=Web Response No relevant relationships by David Moore, source=Web Response No relevant relationships by Rahul Sampath, source=Web Response No relevant relationships by Ly Tran, source=Web Response

Prioritisation of ICU treatments for critically ill patients in a COVID-19 pandemic with scarce resources

BackgroundRelying on capacity increases and patient transfers to deal with the huge and continuous inflow of COVID-19 critically ill patients is a strategy limited by finite human and logistical resources. RationalePrioritising both critical care initiation and continuation is paramount to save the greatest number of lives. It enables to allocate scarce resources in priority to those with the highest probability of benefiting from them. It is fully ethical provided it relies on objective and widely shared criteria, thus preventing arbitrary decisions and guaranteeing equity. Prioritisation seeks to fairly allocate treatments, maximise saved lives, gain indirect life benefits from prioritising exposed healthcare and similar workers, give priority to those most penalised as a last resort, and apply similar prioritisation schemes to all patients. Prioritisation strategyPrioritisation schemes and their criteria are adjusted to the level of resource scarcity: strain (level A) or saturation (level B). Prioritisation yields a four level priority for initiation or continuation of critical care: P1–high priority, P2–intermediate priority, P3–not needed, P4–not appropriate. Prioritisation schemes take into account the patient's wishes, clinical frailty, pre-existing chronic condition, along with severity and evolution of acute condition. Initial priority level must be reassessed, at least after 48h once missing decision elements are available, at the typical turning point in the disease's natural history (ICU days 7 to 10 for COVID-19), and each time resource scarcity levels change. For treatments to be withheld or withdrawn, a collegial decision-making process and information of patient and/or next of kin are paramount. PerspectivePrioritisation strategy is bound to evolve with new knowledge and with changes within the epidemiological situation.

Abstract TP401: Red Cell Distribution Width Predicts Prognosis of Stroke-Associated Infection in Patients With Acute Ischemic Stroke

Purpose: The red cell distribution width (RDW) is a rapid, inexpensive laboratory test. Elevated RDW values are associated with poor outcomes in adult critical illness, especially in cardiovascular disease and infection. We examined the association between RDW and stroke-associated infection, need for critical care and infection-related in-hospital mortality in ischemic stroke. Methods: A consecutive 1,973 patients who were admitted within 7 days after ischemic stroke onset between March 2010 and September 2016 were included for analysis. The patients were categorized into two groups on the basis of RDW(>14.0%). We evaluated the stroke-associated infection, initiation of critical care and infection-related in-hospital mortality using a combination of clinical assessment, radiological imaging and appropriate microbiological tests. Logistic regression was used to identify risk factors for stroke-associated infection, need for critical care and infection-related in-hospital mortality. Results: The patients were divided into two groups according to RDW scores identified as RDW above group (n=342, 17.3%) with mean age 71±11.2 years; 58.8% males and RDW below group (n=1631, 81.7%) with mean age 67±12.5 years; 61.2% males. As expected, the patients with stroke-associated infection were older and more likely to have atrial fibrillation, history of diabetes mellitus, higher NIHSS on admission and higher RDW (19.0% vs 8.2%, p <0.001). The stroke-associated infection rate was higher in the RDW above groups as compared to RDW below group with odds ratio 2.279; confidence interval 1.637 to 3.173; p <0.001, even after adjustment for traditional cardiovascular risk factors . Similar significant robust associations post multivariable adjustments are seen with critical care initiation as well as infection-related in-hospital mortality : odds ratio 1.166; confidence interval 1.054 to 1.290; p =0.003, odds ratio 1.194; confidence interval 1.010 to 1.412; p =0.038, respectively. Conclusion: This study demonstrated that higher RDW predicted stroke-associated infection and its prognosis in patients with acute ischemic stroke. This study has shown that RDW provides additive prognostic data for infection of patients with acute ischemic stroke.

Nucleated red blood cells, critical illness survivors and postdischarge outcomes: a cohort study

BackgroundLittle is known about risk factors associated with out-of-hospital outcomes in survivors of critical illness. We hypothesized that the presence of nucleated red blood cells in patients who survived critical care would be associated with adverse outcomes following hospital discharge.MethodsWe performed a two-center observational cohort study of patients treated in medical and surgical intensive care units in Boston, Massachusetts. All data were obtained from the Research Patient Data Registry at Partners HealthCare. We studied 2878 patients, age ≥ 18 years, who received critical care between 2011 and 2015 and survived hospitalization. The exposure of interest was nucleated red blood cells occurring from 2 days prior to 7 days after critical care initiation. The primary outcome was mortality in the 90 days following hospital discharge. Secondary outcome was unplanned 30-day hospital readmission. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both nucleated red blood cells and outcome. Adjustment included age, race (white versus nonwhite), gender, Deyo–Charlson Index, patient type (medical versus surgical), sepsis and acute organ failure.ResultsIn patients who received critical care and survived hospitalization, the absolute risk of 90-day postdischarge mortality was 5.9%, 11.7%, 15.8% and 21.9% in patients with 0/μl, 1–100/μl, 101–200/μl and more than 200/μl nucleated red blood cells respectively. Nucleated red blood cells were a robust predictor of postdischarge mortality and remained so following multivariable adjustment. The fully adjusted odds of 90-day postdischarge mortality in patients with 1–100/μl, 101–200/μl and more than 200/μl nucleated red blood cells were 1.77 (95% CI, 1.23–2.54), 2.51 (95% CI, 1.36–4.62) and 3.72 (95% CI, 2.16–6.39) respectively, relative to patients without nucleated red blood cells. Further, the presence of nucleated red blood cells is a significant predictor of the odds of unplanned 30-day hospital readmission.ConclusionIn critically ill patients who survive hospitalization, the presence of nucleated red blood cells is a robust predictor of postdischarge mortality and unplanned hospital readmission.

Elevated red cell distribution width at initiation of critical care is associated with mortality in surgical intensive care unit patients

PurposeRecent evidence suggests that red cell distribution width (RDW) is associated with mortality in mixed cohorts of critically ill patients. Our goal was to investigate whether elevated RDW at initiation of critical care in the intensive care unit (ICU) is associated with 90-day mortality in surgical patients. MethodsWe performed a retrospective, single-center cohort study. Normal RDW was defined as 11.5%–14.5%. To investigate the association of admission RDW with 90-day mortality, we performed a logistic regression analysis, controlling for age, sex, race, body mass index, Nutrition Risk Screening 2002 score, Acute Physiology and Chronic Health Evaluation II score, hospital length of stay, as well as levels of creatinine, albumin, and mean corpuscular volume. Results500 patients comprised the analytic cohort; 47% patients had elevated RDW and overall 90-day mortality was 28%. Logistic regression analysis demonstrated that patients with elevated RDW had a greater than two-fold increased odds of mortality (OR 2.28: 95%CI 1.20–4.33) compared to patients with normal RDW. ConclusionsElevated RDW at initiation of care is associated with increased odds of 90-day mortality in surgical ICU patients. These data support the need for prospective studies to determine whether RDW can improve risk stratification in surgical ICU patients.

Clinical and microbiological outcome in septic patients with extremely low 25-hydroxyvitamin D levels at initiation of critical care

A relationship between vitamin D status and mortality in patients in intensive care units (ICU) has been documented. The present study aims to describe the clinical profile and sepsis-related outcome of critically ill septic patients with extremely low (<7 ng/mL) vitamin D levels at ICU admission. We conducted an observational study in the ICU of a teaching hospital including all patients admitted with severe sepsis/septic shock and undergoing 25-hydroxyvitamin D (25(OH)D) testing within the first 24 hours from admission. We studied 107 patients over 12 months. At ICU admission vitamin D deficiency (≤20 ng/mL) was observed in 93.5% of the patients: 57 (53.3%) showed levels <7 ng/mL. As primary outcome, sepsis-related mortality rate was higher in patients with vitamin D levels <7 ng/mL (50.9% versus 26%). Multivariate regression analysis showed that vitamin D concentration <7 ng/mL on ICU admission (p 0.01) and higher mean SAPS II (p <0.01) score were independent predictors of sepsis-related mortality. Patients with very low vitamin D levels suffered higher rate of microbiologically confirmed infections but a lower percentage of microbiological eradication with respect to patients whose values were >7 ng/mL (80.7% versus 58%, p 0.02; 35.3% versus 68%; p 0.03, respectively). Post hoc analysis showed that, in the extremely low vitamin D group, the 52 patients with pneumonia showed a longer duration of mechanical ventilation (9 days (3.75–12.5 days) versus 4 days (2–9 days), p 0.04) and the 66 with septic shock needed vasopressor support for a longer period of time (7 days (4–10 days) versus 4 days (2–7.25 days), p 0.02). Our results suggest that in critical septic patients extremely low vitamin D levels on admission may be a major determinant of clinical outcome. Benefits of vitamin D replacement therapy in this population should be elucidated.

Association between blood alcohol concentration and mortality in critical illness

ObjectiveIn animal models of renal, intestinal, liver, cardiac, and cerebral ischemia, alcohol exposure is shown to reduce ischemia-reperfusion injury. Inpatient mortality of trauma patients is shown to be decreased in a dose-dependent fashion relative to blood alcohol concentration (BAC) at hospital admission. In this study, we examined the association between BAC at hospital admission and risk of 30-day mortality in critically ill patients. DesignWe performed a 2-center observational study of patients treated in medical and surgical intensive care units in Boston, Massachusetts. SettingMedical and surgical intensive care units in 2 teaching hospitals in Boston, Massachusetts. PatientsWe studied 11850 patients, 18 years or older, who received critical care between 1997 and 2007. The exposure of interest was the BAC determined in the first 24 hours of hospital admission and categorized a priori as BAC less than 10 mg/dL (below level of detection), 10 to 80 mg/dL, 80 to 160 mg/dL, and greater than 160 mg/dL. The primary outcome was all-cause mortality in the 30 days after critical care initiation. Secondary outcomes included 90- and 365-day mortality after critical care initiation. Mortality was determined using the US Social Security Administration Death Master File, and 365-day follow-up was present in all cohort patients. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both BAC and mortality. Adjustment included age, sex, race (white or nonwhite), type (surgical vs medical), Deyo-Charlson index, sepsis, acute organ failure, trauma, and chronic liver disease. ResultsThirty-day mortality of the cohort was 13.7%. Compared to patients with BAC levels less than 10 mg/dL, patients with levels greater than or equal to 10 mg/dL had lower odds of 30-day mortality; for BAC levels 10 to 79.9 mg/dL, the OR was 0.53 (95% confidence interval [CI], 0.40-0.70); for BAC levels 80 to 159.9 mg/dL, it was 0.36 (95% CI, 0.26-0.49); and for BAC levels greater than or equal to 160 mg/dL, it was 0.35 (95% CI, 0.27-0.44). After multivariable adjustment, the OR of 30-day mortality was 0.97 (0.72-1.31), 0.79 (0.57-1.10), and 0.69 (0.54-0.90), respectively. When the cohort was analyzed with sepsis as the outcome of interest, the multivariable adjusted odds of sepsis in patients with BAC 80 to 160 mg/dL or greater than 160 mg/dL were 0.72 (0.50-1.04) or 0.68 (0.51-0.90), respectively, compared to those with BAC less than 10 mg/dL. In a subset of patients with blood cultures drawn (n = 4065), the multivariable adjusted odds of bloodstream infection in patients with BAC 80 to 160 mg/dL or greater than 160 mg/dL were 0.53 (0.27-1.01) or 0.49 (0.29-0.83), respectively, compared to those with BAC less than 10 mg/dL. ConclusionsAnalysis of 11850 adult patients showed that having a detectable BAC at hospitalization was associated with significantly decreased odds of 30-day mortality after critical care. Furthermore, BAC greater than 160 mg/dL is associated with significantly decreased odds of developing sepsis and bloodstream infection.

The association of acute kidney injury in the critically ill and postdischarge outcomes: a cohort study*.

Hospital readmissions contribute significantly to the cost of inpatient care and are targeted as a marker for quality of care. Little is known about risk factors associated with hospital readmission in survivors of critical illness. We hypothesized that acute kidney injury in patients who survived critical care would be associated with increased risk of 30-day postdischarge hospital readmission, postdischarge mortality, and progression to end-stage renal disease. Two center observational cohort study. Medical and surgical ICUs at the Brigham and Women's Hospital and the Massachusetts General Hospital in Boston, Massachusetts. We studied 62,096 patients, 18 years old and older, who received critical care between 1997 and 2012 and survived hospitalization. None : All data was obtained from the Research Patient Data Registry at Partners HealthCare. The exposure of interest was acute kidney injury defined as meeting Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease Risk, Injury or Failure criteria occurring 3 days prior to 7 days after critical care initiation. The primary outcome was hospital readmission in the 30 days following hospital discharge. The secondary outcome was mortality in the 30 days following hospital discharge. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both acute kidney injury and readmission status. Adjustment included age, race (white vs nonwhite), gender, Deyo-Charlson Index, patient type (medical vs surgical) and sepsis. Additionally, long-term progression to End Stage Renal Disease in patients with acute kidney injury was analyzed with a risk-adjusted Cox proportional hazards regression model. The absolute risk of 30-day readmission was 12.3%, 19.0%, 21.2%, and 21.1% in patients with No Acute Kidney Injury, Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Injury, and Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Failure, respectively. In patients who received critical care and survived hospitalization, acute kidney injury was a robust predictor of hospital readmission and post-discharge mortality and remained so following multivariable adjustment. The odds of 30-day post-discharge hospital readmission in patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, or Failure fully adjusted were 1.44 (95% CI, 1.25-1.66), 1.98 (95% CI, 1.66-2.36), and 1.55 (95% CI, 1.26-1.91) respectively, relative to patients without acute kidney injury. Further, the odds of 30-day post-discharge mortality in patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, or Failure fully adjusted per our primary analysis were 1.39 (95% CI, 1.28-1.51), 1.46 (95% CI, 1.30-1.64), and 1.42 (95% CI, 1.26-1.61) respectively, relative to patients without acute kidney injury. The addition of the propensity score to the multivariable model did not change the point estimates significantly. Finally, taking into account age, gender, race, Deyo-Charlson Index, and patient type, we observed a relationship between acute kidney injury and development of end-stage renal disease. Patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, Failure experienced a significantly higher risk of end-stage renal disease during follow-up than patients without acute kidney injury (hazard ratio, 2.03; 95% CI, 1.56-2.65; hazard ratio, 3.99; 95% CI, 3.04-5.23; hazard ratio, 10.40; 95% CI, 8.54-12.69, respectively). Patients who suffer acute kidney injury are among a high-risk group of ICU survivors for adverse outcomes. In patients treated with critical care who survive hospitalization, acute kidney injury is a robust predictor of subsequent unplanned hospital readmission. In critical illness survivors, acute kidney injury is also associated with the odds of 30-day postdischarge mortality and the risk of subsequent end-stage renal disease.

Low serum 25-hydroxyvitamin D at critical care initiation is associated with sepsis and morbidity in Dutch critically ill patients

Vitamin D deficiency may frequently occur in critically ill patients and may be associated with sepsis and increased mortality. We therefore evaluated the prevalence of 25-hydroxyvitamin D deficiency in a Dutch ICU, and its relationship with sepsis, morbidity and mortality.

0474. Circulating mitochondrial dna and vitamin d in critical illness

Of the cohort patients studied, 37% were women and 84% were white. The mean age at critical care initiation was 53.5 years (SD 14.2). The mean APACHE II score was 24.5 (SD 8.3), while 100% of the cohort had SIRS, 71% had a source of infection identified and 18% had ARDS. The mean plasma 25(OH)D was 20.6 (SD 11.4) and 28.6% of the study cohort had plasma 25(OH)D ≤ 15 ng/mL. Gross unadjusted 30-day mortality was 26.5%. The mean (SD) plasma 25(OH)D was significantly higher in patients with mtDNA < 4000 copies/ml [25(OH)D 22.0 (11.2) ng/ml] relative to those with mtDNA ≥ 4000 copies/ml [25(OH)D 14.9 (10.9) ng/mL]; P < 0.001. When the cohort was analyzed with the exposure as plasma 25(OH)D and the outcome as plasma mtDNA ≥ 4000 copies/ml, we find that patients with plasma 25(OH)D < 15 ng/mL have a significantly higher odds of having plasma mtDNA ≥ 4000 copies/ml (unadjusted OR= 7.50, 95% CI 1.53-36.79; P=0.013). 25(OH)D in the cohort remains a significant predictor of plasma mtDNA ≥ 4000 copies/ml following adjustment for age, gender, race and APACHE II (adjusted OR= 13.19, 95% CI 1.69-103.34; P=0.014). Cox proportional hazard multivariable regression modeling, adjusting for ap rioridefined covariates comprising APACHE II score, age, sex, race, and plasma 25(OH)D, showed that mtDNA was predictive of all cause mortality following critical care (HR, 4.02; 95% CI, 1.14-14.20 ng/ml). Conclusions 25(OH)D levels are associated with circulating mtDNA levels. This study cannot determine a relationship between 25(OH)D and mtDNA beyond association but raises the question as to whether vitamin D-mediated pathways might play a role in linking autophagic and inflammasome processes.

Prospective Study of Vitamin D Status at Initiation of Care in Critically Ill Surgical Patients and Risk of 90-Day Mortality*

1) To characterize vitamin D status at initiation of critical care in surgical ICU patients and 2) to determine whether this vitamin D status is associated with the risk of prolonged hospital length of stay, 90-day readmission, and 90-day mortality. Prospective cohort study. A teaching hospital in Boston, MA. Hundred surgical ICU patients. None. Mean (± SD) serum total 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were 17 ± 8 ng/mL and 32 ± 19 pg/mL, respectively. Mean calculated bioavailable 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were 2.5 ± 2.0 ng/mL and 6.6 ± 5.3 pg/mL, respectively. Receiver-operating characteristic curve analysis demonstrated that all of four vitamin D measures predicted the three clinical outcomes; total 25-hydroxyvitamin D was not inferior to the other measures. Median (interquartile range) hospital length of stay was 11 days (8-19 d). Poisson regression analysis, adjusted for biologically plausible covariates, demonstrated an association of total 25-hydroxyvitamin D with hospital length of stay (incident rate ratio per 1 ng/mL, 0.98; 95% CI, 0.97-0.98). The 90-day readmission and mortality rates were 24% and 22%, respectively. Even after adjustment for biologically plausible covariates, there remained significant associations of total 25-hydroxyvitamin D with readmission (odds ratio per 1 ng/mL, 0.84; 95% CI, 0.74-0.95) and mortality (odds ratio per 1 ng/mL, 0.84; 95% CI, 0.73-0.97). Serum 25-hydroxyvitamin D levels within 24 hours of ICU admission may identify patients at high risk for prolonged hospitalization, readmission, and mortality. Randomized trials are needed to assess whether vitamin D supplementation can improve these clinically relevant outcomes in surgical ICU patients.

Association of Low Serum 25-Hydroxyvitamin D Levels and Sepsis in the Critically Ill

We hypothesized that deficiency in 25-hydroxyvitamin D prior to hospital admission would be associated with sepsis in the critically ill. Two-center observational study of patients treated in medical and surgical ICUs. Two hundred nine medical and surgical intensive care beds in two teaching hospitals in Boston, MA. Three thousand three hundred eighty-six patients, 18 years old or older, in whom 25-hydroxyvitamin D was measured prior to hospitalization between 1998 and 2011. None. : Preadmission 25-hydroxyvitamin D was categorized as deficiency in 25-hydroxyvitamin D (≤ 15 ng/mL), insufficiency (15-30 ng/mL), and sufficiency (≥ 30 ng/mL). The primary outcome was sepsis as defined by International Classification of Diseases, 9th Edition, Clinical Modification and validated by the 2001 Society of Critical Care Medicine/European Society of Intensive Care Medicine, American College of Chest Physicians, American Thoracic Society, and Surgical Infection Society international sepsis definitions conference guidelines. Logistic regression examined the presence of sepsis 3 days prior to critical care initiation to 7 days after critical care initiation. Adjusted odds ratios were estimated by multivariable logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive for the risk of sepsis. In the full cohort, 25-hydroxyvitamin D deficiency is a significant predictor for the risk of International Classification of Diseases, 9th Edition, Clinical Modification-defined sepsis following multivariable adjustment, including age, gender, race, type (surgical vs medical), and Deyo-Charlson index (adjusted odds ratio, 1.51 [95% CI, 1.17-1.94]; p = 0.001) relative to patients with 25-hydroxyvitamin D sufficiency. In a subset of cohort patients enriched for those with International Classification of Diseases, 9th Edition, Clinical Modification-diagnosed sepsis (n = 444), preadmission 25-hydroxyvitamin D deficiency is a significant predictor for the risk of conference guideline-defined sepsis following multivariable adjustment, including age, gender, race, type (surgical vs medical), and Acute Physiology and Chronic Health Evaluation II (adjusted odds ratio, 2.05 [95% CI, 1.19-3.52]; p = 0.009) relative to patients with 25-hydroxyvitamin D sufficiency. Furthermore, in cohort patients with International Classification of Diseases, 9th Edition, Clinical Modification-defined sepsis (n = 568), the multivariable adjusted risk of 90-day mortality was 1.6-fold higher in those with preadmission 25-hydroxyvitamin D values in the insufficient and deficient range, compared with those with preadmission vitamin D sufficiency (adjusted odds ratio, 1.63 [95% CI, 1.11-2.39]; p = 0.01). 25-hydroxyvitamin D deficiency prior to hospital admission is a significant predictor of sepsis in the critically ill. Additionally, patients with sepsis who are not vitamin D sufficient have an increased risk of mortality following critical care initiation.

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Introduction: Hospital readmission within 30 days of discharge occurs in 18% of Medicare beneficiaries and results in an annual cost of $15 billion. Little is known regarding risk factors associated with hospital readmission in critical illness survivors. Whether malnutrition at critical care initiation has prognostic implications for ICU survivors has not been studied. Methods: We performed a single center observational study of patients treated in medical and surgical intensive care units in Boston, Massachusetts. We studied 3,166 patients, age 18 years or higher, who received critical care, survived hospitalization and received a formal standardized evaluation by a Registered Dietitian from the Department of Nutrition at the Brigham and Women’s Hospital between 2004 and 2011. The exposure of interest, malnutrition was considered to be present if the patient was formally diagnosed by a Registered Dietitian with any of the following: nonspecific protein-calorie malnutrition, protein-calorie malnutrition (mild protein-calorie malnutrition, moderate protein-calorie malnutrition, severe protein-calorie malnutrition, or marasmus). Patients were not considered to have to have malnutrition if diagnosed as “not at risk” or “at risk” for developing malnutrition. We included formal Registered Dietitian evaluations from 10 days prior to critical care initiation or up to 2 days after critical care initiation. The primary outcome was unplanned hospital readmission to the Brigham and Women’s or Massachusetts General Hospitals in the 30 days following hospital discharge. The first hospitalization associated with critical care is identified as the index critical care exposure, and a 30-day unplanned readmission was defined as a subsequent unplanned admission to the hospitals under study within 30 days of discharge following the hospitalization associated with the index critical care exposure. Readmissions with DRG codes commonly associated with planned readmissions were excluded. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both nutrition status and mortality post hospital discharge. Adjustments included age, race, gender, Deyo-Charlson Index, patient type (medical versus surgical), sepsis and number of organs with acute failure. Results: Nonspecific malnutrition was recorded in 49.4%, specific malnutrition in 11.5%, and malnutrition was absent in 39.1%. The 30-day post discharge hospital readmission rate was 19.1%. In patients who received critical care and survived hospitalization, specific protein-calorie malnutrition was a robust predictor of 30-day post discharge hospital readmission and remained so following multivariable adjustment. The odds of 30-day post discharge hospital readmission in patients with nonspecific or specific protein-calorie malnutrition were 1.15 (95%CI, 0.94,1.39) and 1.82 (95%CI, 1.38,2.40) compared to that of patients without malnutrition. Specific protein-calorie malnutrition remained a significant predictor of the odds of 30-day post discharge hospital readmission after adjustment for age, sex, race, Deyo-Charlson Index, sepsis and medical/surgical patient type. The adjusted odds of 30-day post discharge hospital readmission in patients with nonspecific or specific protein-calorie malnutrition were 1.13 (95%CI, 0.93,1.38) and 1.73 (95%CI, 1.31,2.28) respectively compared to that of patients without malnutrition. Conclusions: In a large population of adult critical illness survivors, malnutrition near ICU admission is a robust predictor of all cause mortality following hospital discharge. With heightening societal and political interest in cost-effective healthcare delivery, malnutrition may be a prognostic and potentially modifiable marker for patients who are at high risk for unplanned hospital readmission.

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Introduction: Hospital readmissions contribute significantly to the cost of inpatient care and are targeted as a marker for quality of care. Little is known about risk factors associated with hospital readmission in survivors of critical illness. Methods: We studied 62,587 patients, age ≥ 18 years, who received critical care between 1997 and 2012 and survived hospitalization. The exposure of interest was acute kidney injury (AKI) defined as meeting RIFLE Risk, Injury or Failure criteria occurring 3 days prior to 7 days after critical care initiation. Patients with end stage renal disease prior to critical care initiation were identified by submitting the administrative data to the United States Renal Data System and excluded. In patients whom developed end stage renal disease following an AKI episode, the date chronic dialysis began was recorded. The primary outcome was unplanned hospital readmission in the 30 days following hospital discharge. The first hospitalization associated with critical care is identified as the index critical care exposure, and a 30-day unplanned readmission was defined as a subsequent unplanned admission to the hospitals under study within 30 days of discharge following the hospitalization associated with the index critical care exposure. Readmissions with DRG codes commonly associated with planned readmissions were excluded. The secondary outcome was mortality in the 30 days following hospital discharge. Information on vital status for the study cohort was obtained from the Social Security Administration Death Master File. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both AKI and readmission status. Adjustment included age, race (white versus non-white), gender, Deyo-Charlson Index, patient type (medical versus surgical) and sepsis. Additionally, long-term progression to End Stage Renal Disease in patients with AKI was analyzed with a risk-adjusted Cox proportional hazards regression model. Results: Most cohort patients were men (60%) and white (78%). 48% had medically related DRGs. The mean age at hospital admission was 57 (SD 18) years. 30-day post-discharge hospital readmission rate was 13% and the 30-day post-discharge mortality rate was 3%. In patients who received critical care and survived hospitalization, AKI was a robust predictor of unplanned hospital readmission and post-discharge mortality and remained so following multivariable adjustment. The odds of 30-day post-discharge hospital readmission in patients with RIFLE class Risk, Injury or Failure fully adjusted were 1.44 (95%CI, 1.25, 1.66), 1.98 (95%CI, 1.66, 2.36), and 1.55 (95%CI, 1.26, 1.91) respectively, relative to patients without AKI. Further, the odds of 30-day post-discharge mortality in patients with RIFLE class Risk, Injury or Failure fully adjusted per our primary analysis were 1.39 (95%CI, 1.28, 1.51), 1.46 (95%CI, 1.30, 1.64), and 1.42 (95%CI, 1.26, 1.61) respectively, relative to patients without AKI. Finally, taking into account age, gender, race, Deyo-Charlson Index, and patient type (medical versus surgical), we observed a relationship between AKI and development of End Stage Renal Disease. Patients with RIFLE class Risk, Injury, Failure experienced a significantly higher risk of End Stage Renal Disease during follow-up than patients without acute kidney injury (HR 2.03, 95% CI, 1.56, 2.65; HR 3.99, 95%CI, 3.04, 5.23; HR 10.40, 95%CI, 8.54, 12.69 respectively). Conclusions: Patients who suffer acute kidney injury during critical illness are among a high-risk group of ICU survivors for adverse outcomes. In patients treated with critical care who survive hospitalization, acute kidney injury is a robust predictor of subsequent unplanned hospital readmission. In critical illness survivors, acute kidney injury is also associated with the odds of 30-day post-discharge mortality and the risk of subsequent End Stage Renal Disease.

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Introduction: The relationship between iron and infection has been investigated in Dialysis patients who are at a high risk for infection. Little is known about the relationship between serum iron status and adverse outcomes in critically ill patients. Methods: We performed a two center observational study of patients treated in medical and surgical intensive care units in Boston, Massachusetts. All data was obtained from the Research Patient Data Registry at Partners HealthCare. We studied 4,703 patients, age ≥ 18 years, who received critical care between 1997 and 2011 who had serum iron levels measured within a year prior to hospital admission. Patients with end stage renal disease prior to critical care initiation were identified by submitting the administrative data to the United States Renal Data System and excluded due to high prevalence of both intravenous iron supplementation and bloodstream infection in this population The exposure of interest was serum iron categorized a priori as 0–59.9 μg/dL, 60–169.9 μg/dL (referent) and > 170 μg/dL. The primary outcome was bloodstream infection determined by positive blood culture in the 48 hours prior to ICU admission to 48 hours after ICU admission. Secondary outcomes included sepsis and 30-day mortality. Sepsis was defined by ICD-9-CM and validated by the 2001 SCCM/ESICM, ACCP, ATS, SIS international sepsis definitions conference guidelines. Information on vital status for the study cohort was obtained from the Social Security Administration Death Master File which has high sensitivity and specificity for mortality. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both serum iron and bloodstream infection. Adjustment included age, race, gender, comorbidities (Deyo-Charlson Index) and patient type (medical versus surgical). Results: The majority of patients were men (55%), white (78%) and had medical related DRGs (71%). The mean (SD) age at ICU admission was 63.9 (16.1) years. 243 (5%) patients had pre-hospital iron levels > 170 μg/dL. The cohort bloodstream infection rate was 18.4%, with 35.2% of patients diagnosed with sepsis, and an all cause 30-day mortality rate of 23.5%. Pre-hospital serum iron was a robust predictor of bloodstream infection and remained so following multivariable adjustment. Patients with pre-hospital serum iron > 170 μg/dL have an OR for bloodstream infection of 1.38 (95%CI, 1.00, 1.92, p=0.050) and an adjusted OR of 1.41 (95%CI, 1.01, 1.97, p=0.041) relative to patients with serum iron 60–169.9 μg/dL. Pre-hospital serum iron 0–59.9 μg/dL was not associated with increased odds of bloodstream infection relative to patients with serum iron 60–169.9 μg/dL. Further, patients with pre-hospital serum iron > 170 μg/dL have an OR for sepsis of 1.39 (95%CI, 1.05, 1.84, p=0.022) following adjustment for age, gender, race, patient type and Deyo-Charson index, relative to patients with serum iron 60–169.9 μg/dL. Patients with pre-hospital serum iron > 170 μg/dL have an OR for 30-day mortality of OR of 1.42 (95%CI, 1.02, 1.96, p=0.035) following adjustment for age, gender, race, patient type, Deyo-Charson index and acute organ failure, relative to patients with serum iron 60–169.9 μg/dL. Conclusions: In critically ill patients, an elevated serum iron >170 μg/dL prior to hospitalization is a robust predictor of the development of bloodstream infection, sepsis and 30-day mortality following ICU admission. If our findings are corroborated, information regarding iron metabolism and its relationship to infection in the critically ill may potentially help guide infection management efforts in the ICU.

The Difference Between Critical Care Initiation Anion Gap and Prehospital Admission Anion Gap is Predictive of Mortality in Critical Illness*

We hypothesized that the delta anion gap defined as difference between critical care initiation standard anion gap and prehospital admission standard anion gap is associated with all cause mortality in the critically ill. Observational cohort study. Two hundred nine medical and surgical intensive care beds in two hospitals in Boston, MA. Eighteen thousand nine hundred eighty-five patients, age ≥18 yrs, who received critical care between 1997 and 2007. The exposure of interest was delta anion gap and categorized a priori as <0, 0-5, 5-10, and >10 mEq/L. Logistic regression examined death by days 30, 90, and 365 postcritical care initiation and in-hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. The discrimination of delta anion gap for 30-day mortality was evaluated using receiver operator characteristic curves performed for a subset of patients with all laboratory data required to analyze the data via physical chemical principles (n = 664). None. Delta anion gap was a particularly strong predictor of 30-day mortality with a significant risk gradient across delta anion gap quartiles following multivariable adjustment: delta anion gap <0 mEq/L odds ratio 0.75 (95% confidence interval 0.67-0.81; p < 0.0001); delta anion gap 5-10 mEq/L odds ratio 1.56 (95% confidence interval 1.35-1.81; p < 0.0001); delta anion gap >10 mEq/L odds ratio 2.18 (95% confidence interval 1.76-2.71; p < 0.0001); and all relative to patients with delta anion gap 0-5 mEq/L. Similar significant robust associations post multivariable adjustments are seen with death by days 90 and 365 as well as in-hospital mortality. Correcting for albumin or limiting the cohort to patients with standard anion gap at critical care initiation of 10-18 mEq/L did not materially change the delta anion gap-mortality association. Delta anion gap has similarly moderate discriminative ability for 30-day mortality in comparison to standard base excess and strong ion gap. An increase in standard anion gap at critical care initiation relative to prehospital admission standard anion gap is a predictor of the risk of all cause patient mortality in the critically ill.

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Introduction: The effect of malnutrition on mortality in the critically ill is unclear. Hypothesis: We hypothesize that malnutrition is associated with mortality in critical illness. Methods: We performed a single center prospective cohort study in medical and surgical ICUs in Boston. We studied 7,676 patients, age = 18 years, who received formal evaluation and data collection from a registered dietitian from 2004-2011. The exposure of interest, malnutrition, was present if the patient was diagnosed with non-specific protein-calorie malnutrition or specific protein-calorie malnutrition (mild/moderate/severe protein-calorie malnutrition). Patients not at risk or at risk for malnutrition were considered to not have malnutrition. We included initial dietitian evaluations from 10 days prior to 10 days after critical care initiation. The primary outcome was all cause 30-day mortality. The secondary outcomes were bloodstream infection and sepsis. Associations between nutrition groups and outcomes were estimated by bivariable and multivariable logistic regression models. Results: Nonspecific malnutrition was recorded in 55.9%, specific malnutrition in 12.5%, and malnutrition was absent in 31.6%. The 30-day mortality rate was 19.5%. Nutrition status is associated with 30 day mortality adjusting for age, race, gender, Deyo-Charlson Index, acute organ failure and medical vs surgical patient type: non-specific malnutrition OR = 1.21 (95%CI 1.05-1.39, p=0.01), specific malnutrition OR = 2.08 (95%CI 1.72-2.52, p<.001), all relative to patients without malnutrition. Malnutrition increases the risk of sepsis: non-specific malnutrition OR sepsis = 2.12 (95%CI 1.85-2.45, p<.001), specific malnutrition OR sepsis = 1.93 (95%CI 1.59-2.34, p<.001), all relative to patients without malnutrition, fully adjusted. In patients with blood cultures drawn (n=3,522), malnutrition was associated with bloodstream infection risk (BSI): non-specific malnutrition OR BSI= 1.27 (95%CI 0.96-1.68, p=0.1), specific malnutrition OR BSI = 1.56 (95%CI 1.10-2.22, p=0.01), all relative to patients without malnutrition, fully adjusted. Conclusions: In the critically ill, malnutrition increases the risk of all-cause patient mortality, bloodstream infection and sepsis.