Hours Of ICU Admission Research Articles

Brain death diagnosis in adult for potential cadaveric organ donation in Bangladesh

Aim: The objectives of this study was (i) To increase knowledge of the epidemiological and clinical features of patients diagnosed with brain death for potential cadaveric organ donation (ii) To determine the compliance of guidelines brain death based on neurological criteria (iii) To analyse process of clinical decision making regarding continuation of life support after brain death diagnosis.Materials and Method: A prospective observational study was carried out in a 12 bed adult ICU of a tertiary care hospital with neurosurgery services in Bangladesh over a period of 2 years from January 2015 to December2016. All patients admitted during this period were scrutinized for identification of brain death and impending brain death. They were analyzed for causes of brain death, diagnosis of brain death, and the use of ancillary testing. Potential for organ donation was also kept in mind.Results: During the study period, total 1387 patients were admitted into the study ICU and there were 329 deaths. And out of them 69 were diagnosed as brain death. The main causes of brain death were intracerebral haemorrhage (32/69, 46%), followed by ischemic stroke (11/69, 16%), subarachnoid haemorrhage (11/69, 12%), traumatic brain injury (8/69, 12%) and brain tumor and CNS infection. The diagnosis of brain death was made in 33 (47%) cases in the first 48 hours and 23 (33%) cases in 48-96 hours of ICU admission. With the exception of two cases, all study patients had GCS score ? 8 (97%). Brain death was diagnosed according to American Academy of Neurology (AAN) 2010 guidelines. Only two cases Electroencephalography was done for family request. All life-sustaining measures were withdrawn in 67 (97%) cases with consent of family.Conclusion: There is no scarcity of brain death cases in our country according to our study. We need to promote and popularize the cadaveric organ transplant along with living donor transplantation.Bangladesh Crit Care J March 2017; 5(1): 48-52

Preadmission Oral Corticosteroids Are Associated With Reduced Risk of Acute Respiratory Distress Syndrome in Critically Ill Adults With Sepsis.

To determine the association between preadmission oral corticosteroid receipt and the development of acute respiratory distress syndrome in critically ill patients with sepsis. Retrospective observational study. Medical, surgical, trauma, and cardiovascular ICUs of an academic medical center. A total of 1,080 critically ill patients with sepsis. None. The unadjusted occurrence rate of acute respiratory distress syndrome within 96 hours of ICU admission was 35% among patients who had received oral corticosteroids compared with 42% among those who had not (p = 0.107). In a multivariable analysis controlling for prespecified confounders, preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome in the 96 hours after ICU admission (odds ratio, 0.53; 95% CI, 0.33-0.84; p = 0.008), a finding that persisted in multiple sensitivity analyses. The median daily dose of oral corticosteroids among the 165 patients receiving oral corticosteroids, in prednisone equivalents, was 10 mg (interquartile range, 5-30 mg). Higher doses of preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome (odds ratio for 30 mg of prednisone compared with 5 mg 0.53; 95% CI, 0.32-0.86). In multivariable analyses, preadmission oral corticosteroids were not associated with in-hospital mortality (odds ratio, 1.41; 95% CI, 0.87-2.28; p = 0.164), ICU length of stay (odds ratio, 0.90; 95% CI, 0.63-1.30; p = 0.585), or ventilator-free days (odds ratio, 1.06; 95% CI, 0.71-1.57; p = 0.783). Among ICU patients with sepsis, preadmission oral corticosteroids were independently associated with a lower incidence of early acute respiratory distress syndrome.

Liberal Versus Restrictive Transfusion Strategy in Critically Ill Oncologic Patients: The Transfusion Requirements in Critically Ill Oncologic Patients Randomized Controlled Trial.

To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock. Single center, randomized, double-blind controlled trial. Teaching hospital. Adult cancer patients with septic shock in the first 6 hours of ICU admission. Patients were randomized to the liberal (hemoglobin threshold, < 9 g/dL) or to the restrictive strategy (hemoglobin threshold, < 7 g/dL) of RBC transfusion during ICU stay. Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 [0-3] vs 0 [0-2] unit; p < 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53-1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90 days after randomization, mortality rate in the liberal group was lower (59% vs 70%) than in the restrictive group (hazard ratio, 0.72; 95% CI, 0.53-0.97; p = 0.03). We observed a survival trend favoring a liberal transfusion strategy in patients with septic shock when compared with the restrictive strategy. These results went in the opposite direction of the a priori hypothesis and of other trials in the field and need to be confirmed.

OP21 - Urine partial oxygen pressure as early marker of acute kidney injury after paediatric cardiac surgery

Acute kidney injury (AKI) is the common and serious complication which occurs in open-heart surgery (HS) using cardiopulmonary bypass (CPB). The renal medulla is one the first affected tissues from decreased perfusion during the procedure of cardiopulmonary bypass. Partial pressure of the urine taken from the renal pelvis is related to the perfusion of renal medulla was shown. Neutrophil gelatinase-associated lipocalin (NGAL) is accepted as an early biomarker and a predictor of AKI in a variety of clinical settings. We sought to evaluate the relationship between urine pO2 and kidney function-injury biomarkers and contribution of glycocalyx derangement after paediatric cardiac surgery. Twenty paediatric patients with normal preoperative renal function as assessed by the creatinine level, undergoing HS with CPB were included in this prospective clinical observational study. Besides routine hemodynamics and cerebral tissue oxygen saturation monitoring, patients were assessed for the partial pressure of the bladder urine (PuO2) and renal tissue oxygen saturation monitoring by NIRS intraoperatively (after induction, before CPB, after CPB) and postoperative (admission of ICU, 3rd, 6th, 9th, 12th in ICU) periodically. Additionally, syndecan-1, hyaluronan, cystatin-c, and NGAL levels were measured in plasma and urine samples. PuO2 was found wavy throughout the operation (p>0.05) and increased at the 6th (p<0.05), 9th (p<0.001) and 12th (p<0.001) hours of ICU admission. Renal tissue oxygen saturation (rSO2) monitored by NIRS was found stable throughout the operation and postoperative 12 hours. Plasma NGAL and hyaluronan levels were significantly found to rise at the 12th hour of ICU admission compared to the anaesthesia induction (p<0.001); meanwhile syndecan and cystatin-c were remained constant (p>0.05). A significant correlation between PuO2 and other measurements as renal tissue oxygen saturation (rSO2), arterial blood lactate, NGAL and hyaluronan levels was not determined at any time points. Coexistence of urine pO2 fluctuations and increment of plasma NGAL-hyaluronan levels suggest that urine pO2 could be early marker of kidney injury in paediatric patients undergoing HS. Further investigation in the role of urine pO2 plays in ischemic organ injury and its potential diagnostic implications is needed. 1. Clin Exp Pharmacol Physiol. 2008 Sep;35(9):1109-12

Passive leg raise testing effectively reduces fluid administration in septic shock after correction of non-compliance to test results

BackgroundFluid resuscitation is considered a cornerstone of shock treatment, but recent data have underlined the potential hazards of fluid overload. The passive leg raise (PLR) test has been introduced as one of many strategies to predict ‘fluid responsiveness.’ The use of PLR testing is applicable to a wide range of clinical situations and has the potential to reduce fluid administration, since PLR testing is based upon (reversible) autotransfusion. Despite these theoretical advantages, data on the net effect on fluid balance as a result of PLR testing remain scarce.MethodsWe performed a prospective single-center multi-step interventional study in patients with septic shock to evaluate the effect of implementation of PLR testing on the fluid balance (FB) 48 hours after ICU admission. All patients were equipped with a PiCCO® device for pulse contour analysis to guide fluid administration. An increase in stroke volume (SV) ≥ 10% was considered a positive test result.ResultsBefore introduction of PLR testing, 21 patients were prospectively included in period 1 with a median FB of 4.8 [3.3–7.8]L. After an extensive training program, PLR testing was introduced and 20 patients were included in period 2. Median FB was 4.4 [3.3–7.5]L and did not differ from period 1 (p = 0.72). Further analysis revealed that non-compliance to the PLR test result was 44%. These findings were discussed with all ICU doctors and nurses. By consensus, non-compliance to the PLR test result was identified as the main reason for unsuccessful implementation of PLR testing. After this evaluation, 19 patients were included in period 3 under equal conditions as in period 2. In this period, median FB was 3.1 [1.5–4.9]L and significantly reduced in comparison with periods 1 and 2 (p = 0.016 and p = 0.023, respectively). Non-compliance was 9% and significantly lower than in period 2 (p = 0.009).ConclusionImplementation of PLR testing in patients with septic shock reduced fluid administration in the first 48 hours of ICU admission significantly and substantially. To achieve this endpoint, substantial non-compliance of ICU team members had to be addressed. Fluid administration despite a negative PLR test was the most common form of non-compliance.

Diagnostic and Prognostic Value of Serum Calprotectin in Septic Shock Patients

Calprotectin is a potent acute phase reactant with increases of more than 100 fold during inflamed conditions. We measured the diagnostic and prognostic value of serum calprotectin (SC) in septic shock. We enrolled 50 adult shocked patients admitted to intensive care unit. Then, classified into 2 groups; septic group (25) with well-defined septic shock with positive cultures. Non-septic group (25) with negative cultures or no source of sepsis. Blood samples for SC), C-reactive protein (CRP) and white blood cell count (WBCC) in the first 6 hours of ICU admission and re-obtained again on day 3. We observed the weaning of vasopressor and 7-days in ICU mortality. SC measured on day 1 was significantly higher in the septic group than the non-septic group (p<0.001). SC showed a good correlation with weaning of vasopressor (AUC was 0.764; p<0.028), while it showed relative correlation with 7-days in ICU mortality (AUC was 0.752; p<0.057) compared with other markers in the study. SC may aid in rapid identification of septic shock from non-septic shock at a cutoff of 2 µg/dl (sensitivity 92% and specificity 84%). Also the change in SC level may aid in prognostication of septic shock.

Biomarker Profiling Differentiates Sepsis from Cytokine Release Syndrome in Chimeric Antigen Receptor T-Cell Therapy for Acute Lymphoblastic Leukemia (ALL)

▪Chimeric antigen receptor (CAR)-modified T cells with CD19 specificity (CTL019) are a highly effective novel immune therapy for relapsed/refractory ALL. Cytokine release syndrome (CRS) is the most significant and in some cases a life-threatening toxicity. These patients are often neutropenic and immunosuppressed and at high risk for sepsis. In addition, there have been cases where concurrent infectious complications potentially fueled underlying CRS leading to hypotension and hypoxia refractory to anti-cytokine directed therapies (Frey et al. abstract 2296, ASH 2014). Discriminating between sepsis and CRS can be a significant clinical challenge in the critical time-window required to initiate effective therapy, especially given that the treatments for CRS, including anti-cytokine therapies and corticosteroids, may worsen severe infections. We recently published an extensive study of 43 cytokines and soluble cytokine receptors, and clinical biomarkers in a cohort of 63 CTL019-treated ALL patients. Peak levels of 24 cytokines in the first month after infusion were highly associated with severe CRS, and CRS predictive models were described (Teachey et al. Cancer Discovery, June 1, 2016 6; 664).The object of these current studies was to compare biomarker profiles in CRS and sepsis, and attempt to identify a profile that would discriminate between the two clinical syndromes, particularly at the time of ICU admission. We evaluated 50 cytokines, soluble receptors, and other serum biomarkers in 66 adult and pediatric patients treated with CTL019 and who developed CRS (ALL-CRS cohort), 15 patients not treated with CTL019 but who developed sepsis leading to ICU admission (sepsis cohort), and 10 normal healthy children (control cohort). Of the 66 patients treated with CTL019 and who developed CRS, 30 (45%) required ICU admission. The biomarkers tested included the ones described in our published work plus a panel of seven additional biomarkers (Angiopoietin 2, [ANG2] sCD163, Pentraxin 3 [PTX3], sCD14, PAI-1, P-selectin, ICAM-1) that have previously been reported in the literature to be associated with sepsis.After adjusting for multiple comparisons, the following biomarkers were significantly elevated in sepsis compared to normal subjects: ANG2, GCSF, IFNα, IL1RA, IL4, IL6, MIG, MIP1α, PTX3, TNFα, sCD163, sCD30, sIL-1RI, sIL-1RII, sIL-2Rα, sIL-4R, sRAGE, sTNFRI, sTNFRII, sVEGFR1, sVEGFR2, sVEGFR3, and VEGF, whereas IL13 and RANTES were significantly lower in sepsis. In subjects with ALL and CRS, within 72 hours of ICU admission following CTL019 therapy (N=29), 23 biomarkers were significantly different compared to sepsis after adjusting for multiple comparisons; 16 were elevated in CRS: GM-CSF, HGF, IFN-γ, IFN-α, IL-10, IL-15, IL-5, IL-6, IL-8, IP-10, MCP1, MIG, MIP-1β, sIL-2Rα, sTNFRI, and sTNFRII; whereas 7 were elevated in sepsis subjects: CD163, IL-1β, sCD30, sIL-4R, sRAGE, sVEGFR-1, and sVEGFR-2. Figure 1 shows representative box-plots for sCD163 (elevated in sepsis) and IP-10 (elevated in CRS). Detailed biomarker profiling and an algorithm for discriminating between sepsis and CRS in patients treated with CTL019 will be presented. These comprehensive profiling data provide novel insights into CRS biology and importantly, will help us discriminate between CRS and sepsis in patients who become critically ill after receiving CAR T cell therapy. These data have direct translational therapeutic relevance. [Display omitted] DisclosuresLacey:Novartis: Research Funding. Shaw:Novartis: Research Funding; Vitality Institute: Research Funding. Teachey:Novartis: Research Funding. Weiss:NIGMS K23GM110496: Research Funding; ThermoFisher Scientific: Honoraria; Up-To-Date: Patents & Royalties: Up-To-Date. Chen:Novartis: Research Funding. Frey:Novartis: Research Funding; Amgen: Consultancy. Porter:Genentech: Employment; Novartis: Patents & Royalties, Research Funding. Maude:Novartis: Consultancy. Grupp:Novartis: Consultancy, Research Funding; Pfizer: Consultancy. Pequignot:Novartis: Research Funding. June:Novartis: Honoraria, Patents & Royalties: Immunology, Research Funding; Johnson & Johnson: Research Funding; Celldex: Consultancy, Equity Ownership; Pfizer: Honoraria; Immune Design: Consultancy, Equity Ownership; Tmunity: Equity Ownership, Other: Founder, stockholder ; University of Pennsylvania: Patents & Royalties. Melenhorst:Novartis: Research Funding.

Visual Fixation in the ICU: A Strong Predictor of Long-Term Recovery After Moderate-to-Severe Traumatic Brain Injury.

Posttraumatic amnesia is superior to the initial Glasgow Coma Scale score for predicting traumatic brain injury recovery, but it takes days/weeks to assess. Here, we examined whether return of visual fixation-a potential marker of higher cognitive function-within 24 hours of ICU admission could be used as an early predictor of traumatic brain injury recovery. Two-phase cohort study. Level-I trauma ICU. Moderate-to-severe traumatic brain injury discharged alive between 2010 and 2013. None. Return of visual fixation was assessed through standard behavioral assessments in 181 traumatic brain injury patients who had lost the ability to fixate at ICU admission (phase 1) and compared with posttraumatic amnesia duration and the initial Glasgow Coma Scale score to predict performance on the Glasgow Outcome Scale-Extended 10-40 months after injury (n = 144; phase 2a). A subgroup also completed a visual attention task (n = 35; phase 2b) and a brain MRI after traumatic brain injury (n = 23; phase 2c). With an area under the curve equal to 0.85, presence/absence of visual fixation at 24 hours of ICU admission was found as performant as posttraumatic amnesia (area under the curve, 0.81; difference between area under the curve, 0.04; p = 0.28) for predicting patients' Glasgow Outcome Scale-Extended score. Conversely, the initial Glasgow Coma Scale score was not (area under the curve, 0.63). Even when controlling for age/medication/CT scan findings, fixation remained a significant predictor of Glasgow Outcome Scale-Extended scores (β, -0.29; p < 0.05). Poorer attention performances and greater regional brain volume deficits were also observed in patients who could not fixate at 24 hours of ICU admission versus those who could. Visual fixation within 24 hours of ICU admission could be as performant as posttraumatic amnesia for predicting traumatic brain injury recovery, introducing a new variable of interest in traumatic brain injury outcome research.

Study of Early Elevated Gas6 Plasma Level as a Predictor of Mortality in a Prospective Cohort of Patients with Sepsis.

BackgroundGrowth arrest-specific gene 6 (Gas6), a vitamin K-dependent protein interacting with anionic phospholipids and TAM tyrosine kinase receptors, is elevated in plasma of septic patients. Previous studies did not find different levels between survivors and non-survivors at admission because either they included a low number of patients (<50) or a low number of non-survivors (5%).ObjectivesTo determine, in a larger cohort of septic patients comprising an expected number of non-survivors, the performance of the plasma level of Gas6 and its soluble receptor Axl (sAxl) within 24 hours of admission to predict in-ICU mortality.PatientsSeptic adults with or without shock.MethodsGas6 and sAxl were prospectively measured by ELISA at day 0, 3, 7, and then weekly until discharge or death.ResultsWe evaluated 129 septic patients, including 82 with and 47 without shock, with in-ICU mortality rate of 19.4% and in-hospital mortality rate of 26%. Gas6 level was higher in non-survivors than in survivors (238 vs. 167%, P = 0.003); this difference remained constant during the ICU stay. The area under the ROC curve for Gas6 (0.695 [95% CI: 0.58–0.81]) was higher than for sAxl, procalcitonin, CRP, IL-1beta, IL-6 and-alpha, and slightly higher than for IL-8, IL-10, SOFA and APACHEII scores in predicting in-ICU mortality. Considering 249% as a cut-off value, Gas6 measurement had a negative predictive value for mortality of 87%.ConclusionIt seems that Gas6 plasma level within 24 hours of ICU admission may predicts in-ICU mortality in patients with sepsis. If our result are confirmed in external validation, Gas6 plasma level measurement could contribute to the identification of patients who may benefit most from more aggressive management.

Cumulative Fluid Balance and Mortality in Septic Patients With or Without Acute Kidney Injury and Chronic Kidney Disease.

Incident acute kidney injury and prevalent chronic kidney disease are commonly encountered in septic patients. We examined the differential effect of acute kidney injury and chronic kidney disease on the association between cumulative fluid balance and hospital mortality in critically ill septic patients. Retrospective cohort study. Urban academic medical center ICU. ICU adult patients with severe sepsis or septic shock and serum creatinine measured within 3 months prior to and 72 hours of ICU admission. Patients with estimated glomerular filtration rate less than 15 mL/min/1.73 m or receiving chronic dialysis were excluded. None. A total of 2,632 patients, 1,211 with chronic kidney disease, were followed up until hospital death or discharge. Acute kidney injury occurred in 1,525 patients (57.9%), of whom 679 (44.5%) had chronic kidney disease. Hospital mortality occurred in 603 patients (22.9%). Every 1-L increase in cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality in all patients (adjusted odds ratio, 1.06 [95% CI] 1.04-1.08; p < 0.001), and in each acute kidney injury/chronic kidney disease subgroup (adjusted odds ratio, 1.06 [1.03-1.09] for acute kidney injury+/chronic kidney disease+; 1.09 [1.05-1.13] for acute kidney injury-/chronic kidney disease+; 1.05 [1.03-1.08] for acute kidney injury+/chronic kidney disease-; and 1.07 [1.02-1.11] for acute kidney injury-/chronic kidney disease-). There was a significant interaction between acute kidney injury and chronic kidney disease on cumulative fluid balance (p =0.005) such that different cumulative fluid balance cut-offs with the best prognostic accuracy for hospital mortality were identified: 5.9 L for acute kidney injury+/chronic kidney disease+; 3.8 L for acute kidney injury-/chronic kidney disease+; 4.3 L for acute kidney injury+/chronic kidney disease-; and 1.5 L for acute kidney injury-/chronic kidney disease-. The addition of cumulative fluid balance to the admission Sequential Organ Failure Assessment score had increased prognostic utility for hospital mortality when compared with Sequential Organ Failure Assessment alone, particularly in patients with acute kidney injury. Higher cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality regardless of acute kidney injury or chronic kidney disease presence. We characterized cumulative fluid balance cut-offs associated with hospital mortality based on acute kidney injury/chronic kidney disease status, underpinning the heterogeneity of fluid regulation in sepsis and kidney disease.

Hypothermia in Adult ICUs: Changing Incidence But Persistent Risk Factor for Mortality.

This study examined whether hypothermia (< 36.0°C) incidence among critically ill patients varied over time, the determinants of change, and the associated risk for ICU mortality. Interrupted time series analysis among adults admitted to ICUs in Calgary, Canada over 8.5 years. Changes in the incidence of hypothermia within the first 24 hours of ICU admission were modelled using segmented regression. Among 15,291 first admissions to ICU, hypothermia incidence decreased from 29% to 21% during the study period. Implementation of a new temporal artery thermometer (TAT) was associated with the majority of the decrease in incidence (10%; 95% CI 7.1-13%; P < .0001). However, subgroup analysis revealed important differences between medical and surgical patients. Hypothermia incidence decreased among surgical patients before TAT implementation (0.4% per quarter, 95% CI 0.1-0.7%, P = .009), but not after, whereas in medical patients, the incidence increased after (1.0% per quarter, 95% CI 0.6-1.4%, P < .0001) but not before TAT implementation. Segmented logistic regression suggested that increases in the proportion of patients with non-traumatic neurologic admission diagnoses were associated with hypothermia incidence among medical patients, whereas there was no measurable clinical factor associated with the observed time trends among surgical patients. Hypothermia at ICU admission was independently associated with ICU mortality in medical and surgical patients throughout the entire study. The incidence of hypothermia at ICU admission was dependent on medical versus surgical status, and the method of non-invasive temperature measurement, but was persistently associated with ICU mortality.

Outcomes of Protocol-Driven Care of Critically Ill Severely Anemic Patients for Whom Blood Transfusion Is Not an Option*

To compare the outcomes of severely anemic critically ill patients for whom transfusion is not an option ("bloodless" patients) with transfused patients. Cohort study with propensity score matching. ICU of a referral center. One hundred seventy-eight bloodless and 441 transfused consecutive severely anemic, critically ill patients, admitted between May 1996 and April 2011, and having at least one hemoglobin level less than or equal to 8 g/dL within 24 hours of ICU admission. Patients with diagnosis of brain injury, acute myocardial infarction, or status postcardiac surgery were excluded. Allogeneic RBC transfusion during ICU stay. Primary outcome was in-hospital mortality. Other outcomes were ICU mortality, readmission to ICU, new electrocardiographic or cardiac enzyme changes suggestive of cardiac ischemia or injury, and new positive blood culture result. Transfused patients were older, had higher hemoglobin level at admission, and had higher Acute Physiology and Chronic Health Evaluation II score. Hospital mortality rates were 24.7% in bloodless and 24.5% in transfused patients (odds ratio, 1.01; 95% CI, 0.68-1.52; p = 0.95). Adjusted odds ratio of hospital mortality was 1.52 (95% CI, 0.95-2.43; p = 0.08). No significant difference in ICU readmission or positive blood culture results was observed. Analysis of propensity score-matched cohorts provided similar results. Overall risk of mortality in severely anemic critically ill bloodless patients appeared to be comparable with transfused patients, albeit the latter group had older age and higher Acute Physiology and Chronic Health Evaluation II score. Use of a protocol to manage anemia in these patients in a center with established patient blood management and bloodless medicine and surgery programs is feasible and likely to contribute to improved outcome, whereas more studies are needed to better delineate the impact of such programs.

E.04 Coma and delirium are associated with low levels of brain tissue oxygen in critically ill patients

Background: The cause of ICU delirium is unknown. We used near infrared spectroscopy (NIRS) to measure brain tissue oxygenation (BtO2) in critically ill patients, to test the hypothesis that poor cerebral oxygen delivery contributes to ICU delirium. Methods: Adult patients were enrolled if they required mechanical ventilation for &gt;24 hours, and/or vasoactive agents. Patients were excluded if they had previous cognitive dysfunction, brain injury on admission, or a life expectancy &lt;24 hours. BtO2 was measured for the first 24 hours of ICU admission. The confusion assessment method-ICU (CAM-ICU) was used to screen for delirium. Participants were designated to one of three groups on the basis of their predominant neurological status (comatose, delirious, or intact). Results: To date, 47 patients have been recruited. Both delirious and comatose patients’ had significantly lower BtO2 levels compared to intact patients (P&lt;0.001). There was a significant correlation between hemoglobin and BtO2 (R2=0.347, P&lt;0.01). However, when correlation analysis was conducted separately amongst the three groups, the delirious patients (R2=0.485, P&lt;0.05) were the strongest contributors to this positive correlation. Conclusions: Delirious patients exhibited the lowest BtO2 recordings and demonstrated a significant association between Hb and BtO2. This study offers potential insight into the pathophysiology of ICU delirium.

Comparative Effectiveness of Second Vasoactive Agents in Septic Shock Refractory to Norepinephrine.

We aim to identify the appropriate vasoactive agent in patients with septic shock who are refractory to optimal doses of norepinephrine. In this retrospective observational cohort study over a 4-year period, patients who received norepinephrine within 24 hours of ICU admission and a second agent within 48 hours were enrolled. Among 2640 patients screened, 234 patients were enrolled, aged 60.8 ± 17.8 years, Acute Physiology and Chronic Health Evaluation IV 98.3 ± 27.5, 81.6% mechanically ventilated, and 65.8% in-hospital mortality. Within 96 hours, 2.8 ± 1.0 vasoactive agents were administered. Fifty, 50, 66, and 68 patients received dobutamine, dopamine, phenylephrine, and vasopressin as the second agent, with crude in-hospital mortality 40.0%, 66.0%, 74.2%, and 76.5%, respectively, P < .001. Survival analysis showed a statistically significant difference in survival time by second vasoactive agent, P < .001. After adjusting for confounding variables, dobutamine showed significant decreased odds ratio (OR) for mortality compared to vasopressin: OR 0.34 (95% confidence interval 0.14-0.84, P = .04). The relative risk of dying was 55.8% lower in patients receiving dobutamine versus vasopressin, P < .01. Dobutamine is associated with decreased mortality compared to other second vasoactive agents in septic shock when norepinephrine is not sufficient. A prospective randomized trial examining the outcome impact of the second vasoactive agent is needed.

The Development of Intensive Care Unit Acquired Hypernatremia Is Not Explained by Sodium Overload or Water Deficit: A Retrospective Cohort Study on Water Balance and Sodium Handling.

Background. ICU acquired hypernatremia (IAH, serum sodium concentration (sNa) ≥ 143 mmol/L) is mainly considered iatrogenic, induced by sodium overload and water deficit. Main goal of the current paper was to answer the following questions: Can the development of IAH indeed be explained by sodium intake and water balance? Or can it be explained by renal cation excretion? Methods. Two retrospective studies were conducted: a balance study in 97 ICU patients with and without IAH and a survey on renal cation excretion in 115 patients with IAH. Results. Sodium intake within the first 48 hours of ICU admission was 12.5 [9.3–17.5] g in patients without IAH (n = 50) and 15.8 [9–21.9] g in patients with IAH (n = 47), p = 0.13. Fluid balance was 2.3 [1–3.7] L and 2.5 [0.8–4.2] L, respectively, p = 0.77. Urine cation excretion (urine Na + K) was < sNa in 99 out of 115 patients with IAH. Severity of illness was the only independent variable predicting development of IAH and low cation excretion, respectively. Conclusion. IAH is not explained by sodium intake or fluid balance. Patients with IAH are characterized by low urine cation excretion, despite positive fluid balances. The current paradigm does not seem to explain IAH to the full extent and warrants further studies on sodium handling in ICU patients.

The Association Between Low Admission Peak Plasma Creatinine Concentration and In-Hospital Mortality in Patients Admitted to Intensive Care in Australia and New Zealand.

To evaluate the independent association between low peak admission plasma creatinine concentrations and in-hospital mortality in patients requiring critical care in Australia and New Zealand. Multicenter, binational, retrospective cohort study. Data were extracted from the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation adult patient database. All available records for the period 2000 to 2013 were utilized. The following exclusion criteria were applied: all readmission episodes (within the same hospital stay), missing in-hospital mortality, admission post kidney transplantation, chronic renal replacement therapy (hemodialysis or peritoneal dialysis), and missing peak plasma creatinine concentration. Demographic, anthropometric, admission, illness severity, laboratory, and outcome data were then extracted. Patients were categorized on the basis of their peak (maximum) plasma creatinine concentration recorded in the first 24 hours of ICU admission. Illness severity-adjusted associations with in-hospital mortality relative to a reference category of 70-79 μmol/L were then determined using multivariate logistic regression. Nil. Data pertaining to 1,250,449 admissions were available for the study period. Following exclusions, 1,045,718 patients were included. Regression analysis identified that peak plasma creatinine concentrations less than 60 μmol/L measured in the first 24 hours after ICU admission imply a steadily increasing adjusted in-hospital mortality risk. In cases where this value is markedly low (< 30 μmol/L), the adjusted odds of dying in-hospital is over two-fold higher than the reference category and exceeds the risk implied with elevated (≥ 180 μmol/L) values. This finding was also independent of anthropometric data. In a large heterogenous cohort of critically ill patients, low admission peak plasma creatinine concentrations are independently associated with increased risk-adjusted in-hospital mortality. Further research should now focus on the potential mechanisms underpinning this finding, such as a low skeletal muscle mass and/or fluid overload.

Central venous-to-arterial carbon dioxide difference combined with arterial-to-venous oxygen content difference is associated with lactate evolution in the hemodynamic resuscitation process in early septic shock.

IntroductionSince normal or high central venous oxygen saturation (ScvO2) values cannot discriminate if tissue perfusion is adequate, integrating other markers of tissue hypoxia, such as central venous-to-arterial carbon dioxide difference (PcvaCO2 gap) has been proposed. In the present study, we aimed to evaluate the ability of the PcvaCO2 gap and the PcvaCO2/arterial-venous oxygen content difference ratio (PcvaCO2/CavO2) to predict lactate evolution in septic shock.MethodsObservational study. Septic shock patients within the first 24 hours of ICU admission. After restoration of mean arterial pressure, and central venous oxygen saturation, the PcvaCO2 gap and the PcvaCO2/CavO2 ratio were calculated. Consecutive arterial and central venous blood samples were obtained for each patient within 24 hours. Lactate improvement was defined as the decrease ≥ 10% of the previous lactate value.ResultsThirty-five septic shock patients were studied. At inclusion, the PcvaCO2 gap was 5.6 ± 2.1 mmHg, and the PcvaCO2/CavO2 ratio was 1.6 ± 0.7 mmHg · dL/mL O2. Those patients whose lactate values did not decrease had higher PcvaCO2/CavO2 ratio values at inclusion (1.8 ± 0.8vs. 1.4 ± 0.5, p 0.02). During the follow-up, 97 paired blood samples were obtained. No-improvement in lactate values was associated to higher PcvaCO2/CavO2 ratio values in the previous control. The ROC analysis showed an AUC 0.82 (p < 0.001), and a PcvaCO2/CavO2 ratio cut-off value of 1.4 mmHg · dL/mL O2 showed sensitivity 0.80 and specificity 0.75 for lactate improvement prediction. The odds ratio of an adequate lactate clearance was 0.10 (p < 0.001) in those patients with an elevated PcvaCO2/CavO2 ratio (≥1.4).ConclusionIn a population of septic shock patients with normalized MAP and ScvO2, the presence of elevated PcvaCO2/CavO2 ratio significantly reduced the odds of adequate lactate clearance during the following hours.

A Prospective Analysis of Transthyretin Levels at Admission and Changes Over Time in Critically Ill Trauma Patients

Haltmeier, Tobias MD; Inaba, Kenji MD, FACS; Durso, Joseph; Siboni, Stefano MD; Cheng, Vincent; Schnüriger, Beat MD; Benjamin, Elizabeth R. MD, PhD, FACS; Demetriades, Demetrios MD, PhD, FACS Author Information

Assessment of cell-cycle arrest biomarkers to predict early and delayed acute kidney injury.

Purpose. To assess urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein 7 ([TIMP-2]·[IGFBP7]), urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary cystatin-C as acute kidney injury predictors (AKI) exploring the association of nonrenal factors with elevated biomarker levels. Methods. We studied 94 patients with urine collected within 48 hours of ICU admission and no AKI at sampling. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. Predictive performance was assessed by the area under the receiver operating characteristics (ROC) curve. Associations between biomarkers and clinical factors were assessed by multivariate linear regression. Results. Overall, 19 patients (20%) developed AKI within 48 hours. [TIMP-2]·[IGFBP7], NGAL, or cystatin-C admission levels did not differ between patients without AKI and patients developing AKI. [TIMP-2]·[IGFBP7], NGAL, and cystatin-C were poor AKI predictors (ROC areas 0.34–0.51). Diabetes was independently associated with higher [TIMP-2]·[IGFBP7] levels (P = 0.02) but AKI was not (P = 0.24). Sepsis was independently associated with higher NGAL (P < 0.001) and cystatin-C (P = 0.003) levels. Conclusions. Urinary [TIMP-2]·[IGFBP7], NGAL, and cystatin-C should be used cautiously as AKI predictors in general ICU patients since urine levels of these biomarkers are affected by factors other than AKI and their performance can be poor.

Microalbuminuria: A Predictor of Outcome in Critically ill Patients in Intensive Care Units

Background: Diffuse endothelial dysfunction in physical, chemical or infectious insult to the host leads to an increase in systemic capillary permeability. The renal component manifests as Microalbuminuria. The degree of Microalbuminuria correlates with the severity of the acute insult and the quantification of which may serve to predict outcome in critically ill patients. Objectives: To evaluate whether the degree of Microalbuminuria could predict outcome in critically ill patients or not. Settings and Study design: This cohort study was carried out in the 20 bed mixed Medical-Surgical Intensive Care Unit of Dhaka Medical College Hospital. A total 60 patients were purposively recruited for this study. In our study, we included all adult critically ill patients aged 18 years or more admitted in ICU after fulfilling the criteria of critically ill patients and who stayed for more than 24 hours. Patients with pregnancy, menstruation, anuria, macroscopic haematuria, pre-existing kidney disease, were excluded. Spot urine samples were collected by ICU nurses at 24 hrs of admission, for the quantification of Albumin Creatinine Ratio, which was referred to as ACR. The outcome of the patient was classified as death and discharge/ survival. Maximum follow up was done for 15 days. Patients discharged within this 15 days, were considered as survival. Results: Patients were divided into two groups, Group-I: subjects (exposed): Patients having Microalbuminuria. Group-II: control (unexposed): Patients having no Microalbuminuria. In this study, Relative Risk was calculated for risk measurement and to assess the strength of association between the patients having Microalbuminuria and outcome and the calculated relative risk was 2.08. It indicates that the presence of Microalbuminuria is a risk factor for the critically ill patients. Chi-square test was used to compare categorical outcomes and for hypothesis testing. The test statisticis11.94 and p=<0.001.So, our study result supports the hypothesis that Microalbuminuria predicts the outcome in critically ill patients. Conclusion: It was observed that the presence of Microalbuminuria at 24 hours of ICU admission is a predictor of poor outcome in critically ill patients. Absence of Microalbuminuria at 24hrs of admission may help to predict survival in the ICU. So the study concludes that the Microalbuminuria would provide a rapid, simple, inexpensive bedside test to identify patients who may benefit from appropriate early therapeutic strategies. It may prevent further capillary leak and hence the onset of multi organ failure and death. Journal of Bangladesh Society of Anaesthesiologists 2015; 28(1): 12-18