The Influence of Potential Organ Donors on Standardized Mortality Ratios and ICU Benchmarking.

OBJECTIVES: The standardized mortality ratio (SMR) is a common metric to benchmark ICUs. However, SMR may be artificially distorted by the admission of potential organ donors (POD), who have nearly 100% mortality, although risk prediction models may not identify them as high-risk patients. We aimed to evaluate the impact of PODs on SMR. DESIGN: Retrospective registry-based multicenter study. SETTING: Twenty ICUs in Finland, Estonia, and Switzerland in 2015-2017. PATIENTS: Sixty thousand forty-seven ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used a previously validated mortality risk model to calculate the SMRs. We investigated the impact of PODs on the overall SMR, individual ICU SMR and ICU benchmarking. Of the 60,047 patients admitted to the ICUs, 514 (0.9%) were PODs, and 477 (93%) of them died. POD deaths accounted for 7% of the total 6738 in-hospital deaths. POD admission rates varied from 0.5 to 18.3 per 1000 admissions across ICUs. The risk prediction model predicted a 39% in-hospital mortality for PODs, but the observed mortality was 93%. The ratio of the SMR of the cohort without PODs to the SMR of the cohort with PODs was 0.96 (95% CI, 0.93-0.99). Benchmarking results changed in 70% of ICUs after excluding PODs. CONCLUSIONS: Despite their relatively small overall number, PODs make up a large proportion of ICU patients who die. PODs cause bias in SMRs and in ICU benchmarking. We suggest excluding PODs when benchmarking ICUs with SMR.

Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose-associated 90-Day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE III).

Rationale: The SPICE III (Sedation Practice in Intensive Care Evaluation) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation. Objectives: To quantify the association of different infusion rates of dexmedetomidine and propofol, given in combination, with mortality and to determine if this is modified by age. Methods: We included 1,177 patients randomized in SPICE III to receive dexmedetomidine and given supplemental propofol, stratified by age (>65 or ⩽65 yr). We used double stratification analysis to produce quartiles of steady infusion rates of dexmedetomidine while escalating propofol dose and vice versa. We used Cox proportional hazard and multivariable regression adjusted for relevant clinical variable to evaluate the association of sedative dose with 90-day mortality. Measurements and Main Results: Younger patients (598 of 1,177 [50.8%]) received significantly higher doses of both sedatives compared with older patients to achieve comparable sedation depth. On double stratification analysis, escalating infusion rates of propofol to 1.27 mg/kg/h at a steady dexmedetomidine infusion rate (0.54 µg/kg/h) was associated with reduced adjusted mortality in younger but not older patients. This was consistent with multivariable regression modeling (hazard ratio, 0.59; 95% confidence interval, 0.43-0.78; P < 0.0001) adjusted for baseline risk and interaction with dexmedetomidine dose. In contrast, among younger patients, using multivariable regression, escalating dexmedetomidine infusion rate was associated with increased adjusted mortality (hazard ratio, 1.30; 95% confidence interval, 1.03-1.65; P = 0.029). Conclusions: In patients ⩽65 years of age sedated with dexmedetomidine and propofol combination, preferentially increasing the dose of propofol was associated with decreased adjusted 90-day mortality. Conversely, increasing dexmedetomidine may be associated with increased mortality. Clinical trial registered with www.clinicaltrials.gov (NCT01728558).

Variation in Severity-Adjusted Resource use and Outcome for Neurosurgical Emergencies in the Intensive Care Unit.

BACKGROUND: The correlation between the standardized resource use ratio (SRUR) and standardized hospital mortality ratio (SMR) for neurosurgical emergencies is not known. We studied SRUR and SMR and the factors affecting these in patients with traumatic brain injury (TBI), nontraumatic intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS: We extracted data of patients treated in six university hospitals in three countries (2015-2017). Resource use was measured as SRUR based on purchasing power parity-adjusted direct costs and either intensive care unit (ICU) length of stay (costSRURlength of stay) or daily Therapeutic Intervention Scoring System scores (costSRURTherapeutic Intervention Scoring System). Five a priori defined variables reflecting differences in structure and organization between the ICUs were used as explanatory variables in bivariable models, separately for the included neurosurgical diseases. RESULTS: Out of 28,363 emergency patients treated in six ICUs, 6,162 patients (22%) were admitted with a neurosurgical emergency (41% nontraumatic ICH, 23% SAH, 13% multitrauma TBI, and 23% isolated TBI). The mean costs for neurosurgical admissions were higher than for nonneurosurgical admissions, and the neurosurgical admissions corresponded to 23.6-26.0% of all direct costs related to ICU emergency admissions. A higher physician-to-bed ratio was associated with lower SMRs in the nonneurosurgical admissions but not in the neurosurgical admissions. In patients with nontraumatic ICH, lower costSRURs were associated with higher SMRs. In the bivariable models, independent organization of an ICU was associated with lower costSRURs in patients with nontraumatic ICH and isolated/multitrauma TBI but with higher SMRs in patients with nontraumatic ICH. A higher physician-to-bed ratio was associated with higher costSRURs for patients with SAH. Larger units had higher SMRs for patients with nontraumatic ICH and isolated TBI. None of the ICU-related factors were associated with costSRURs in nonneurosurgical emergency admissions. CONCLUSIONS: Neurosurgical emergencies constitute a major proportion of all emergency ICU admissions. A lower SRUR was associated with higher SMR in patients with nontraumatic ICH but not for the other diagnoses. Different organizational and structural factors seemed to affect resource use for the neurosurgical patients compared with nonneurosurgical patients. This emphasizes the importance of case-mix adjustment when benchmarking resource use and outcomes.

The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.

Early Sedation with Dexmedetomidine in Critically Ill Patients.

BACKGROUND: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied. METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from -5 [unresponsive] to +4 [combative]) was -2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days. RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, -2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group. CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group. (Funded by the National Health and Medical Research Council of Australia and others; SPICE III ClinicalTrials.gov number, NCT01728558.).

Association of Sequential Organ Failure Assessment (SOFA) components with mortality.

BACKGROUND: Sequential Organ Failure Assessment (SOFA) is a practical method to describe and quantify the presence and severity of organ system dysfunctions and failures. Some proposals suggest that SOFA could be employed as an endpoint in trials. To justify this, all SOFA component scores should reflect organ dysfunctions of comparable severity. We aimed to investigate whether the associations of different SOFA components with in-hospital mortality are comparable. METHODS: We performed a study based on nationwide register data on adult patients admitted to 26 Finnish intensive care units (ICUs) during 2012-2015. We determined the SOFA score as the maximum score in the first 24 hours after ICU admission. We defined organ failure (OF) as an organ-specific SOFA score of three or higher. We evaluated the association of different SOFA component scores with mortality. RESULTS: Our study population comprised 63,756 ICU patients. Overall hospital mortality was 10.7%. In-hospital mortality was 22.5% for patients with respiratory failure, 34.8% for those with coagulation failure, 40.1% for those with hepatic failure, 14.9% for those with cardiovascular failure, 26.9% for those with neurologic failure and 34.6% for the patients with renal failure. Among patients with comparable total SOFA scores, the risk of death was lower in patients with cardiovascular OF compared with patients with other OFs. CONCLUSIONS: All SOFA components are associated with mortality, but their weights are not comparable. High scores of other organ systems mean a higher risk of death than high cardiovascular scores. The scoring of cardiovascular dysfunction needs to be updated.

Should Vasopressors Be Started Early in Septic Shock?

Sepsis can influence blood volume, its distribution, vascular tone, and cardiac function. Persistent hypotension or the need for vasopressors after volume resuscitation is part of the definition of septic shock. Since increased positive fluid balance has been associated with increased morbidity and mortality in sepsis, timing of vasopressors in the treatment of septic shock seems crucial. However, conclusive evidence on timing and sequence of interventions with the goal to restore tissue perfusion is lacking. The aim of this narrative review is to depict the pathophysiology of hypotension in sepsis, evaluate how common interventions to treat hypotension interfere with physiology, and to give a resume of the results from clinical studies focusing on targets and timing of vasopressor in sepsis. The majority of studies comparing early versus late administration of vasopressors in septic shock are rather small, single-center, and retrospective. The range of "early" is between 1 and 12 hours. The available studies suggest a mean arterial pressure of 60 to 65 mm Hg as a threshold for increased risk of morbidity and mortality, whereas higher blood pressure targets do not seem to add further benefits. The data, albeit mostly from observational studies, speak for combining vasopressors with fluids rather "early" in the treatment of septic shock (within a 0-3-hour window). Nevertheless, the optimal resuscitation strategy should take into account the source of infection, the pathophysiology, the time and clinical course preceding the diagnosis of sepsis, and also comorbidities and sepsis-induced organ dysfunction.

Gas exchange calculation may estimate changes in pulmonary blood flow during veno-arterial extracorporeal membrane oxygenation in a porcine model.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is used as rescue therapy for severe cardiopulmonary failure. We tested whether the ratio of CO2 elimination at the lung and the V-A ECMO (V˙co2ECMO/V˙co2Lung) would reflect the ratio of respective blood flows and could be used to estimate changes in pulmonary blood flow (Q˙Lung), i.e., native cardiac output. Four healthy pigs were centrally cannulated for V-A ECMO. We measured blood flows with an ultrasonic flow probe. V˙co2ECMO and V˙co2Lung were calculated from sidestream capnographs under constant pulmonary ventilation during V-A ECMO weaning with changing sweep gas and/or V-A ECMO blood flow. If ventilation-to-perfusion ratio (V˙/Q˙) of V-A ECMO was not 1, the V˙co2ECMO was normalized to V˙/Q˙ = 1 (V˙co2ECMONorm). Changes in pulmonary blood flow were calculated using the relationship between changes in CO2 elimination and V-A ECMO blood flow (Q˙ECMO). Q˙ECMO correlated strongly with V˙co2ECMONorm (r2 0.95-0.99). Q˙Lung correlated well with V˙co2Lung (r2 0.65-0.89, P < = 0.002). Absolute Q˙Lung could not be calculated in a nonsteady state. Calculated pulmonary blood flow changes had a bias of 76 (-266 to 418) mL/min and correlated with measured Q˙Lung (r2 0.974-1.000, P = 0.1 to 0.006) for cumulative ECMO flow reductions. In conclusion, V˙co2 of the lung correlated strongly with pulmonary blood flow. Our model could predict pulmonary blood flow changes within clinically acceptable margins of error. The prediction is made possible with normalization to a V˙/Q˙ of 1 for ECMO. This approach depends on measurements readily available and may allow immediate assessment of the cardiac output response.

Defense mechanisms to increasing back pressure for hepatic oxygen transport and venous return in porcine fecal peritonitis.

High central venous pressure (CVP) acutely decreases venous return. How this affects hepatic oxygen transport in sepsis remains unclear. The aim of this study was to evaluate the effects of repeated increases in CVP via standard nursing procedures (NPs) on hepato-splanchnic and renal oxygen transport in a prolonged porcine sepsis model. Twenty anesthetized and mechanically ventilated pigs with regional hemodynamics monitored were randomized to fecal peritonitis or controls (n = 10 pigs/group). Resuscitation was started after 8 h of observation and continued for 3 days. NPs were performed at baseline and 8 h, 32 h, 56 h, and 72 h after resuscitation started. NPs increased CVP by 4-7 mmHg in both groups. In controls, this was associated with less decrease in hepatic arterial (Qha; 62 ± 70 mL/min) than portal venous flow (Qpv; 364 ± 151 mL/min). Portal venous oxygen content and hepatic O2 delivery (Do2) and consumption (V̇o2) decreased by 11 ± 6 mL/dL and 0.9 ± 0.3 and 0.4 ± 0.3 mL·min-1·kg-1, respectively. In septic animals, hepatic Do2 decreased more in response to increasing CVP (1.5 ± 0.9 mL·min-1·kg-1), which was attributable to a larger fall in both Qha (88 ± 66 ml/min) and portal O2 content (14 ± 10 mL/dL, all P < 0.05). This resulted in numerically lower hepatic V̇o2 since O2 extraction did not increase significantly. In control conditions, a smaller decrease in Qha compared with Qpv helped to limit the reduction in hepatic V̇o2 in response to acute CVP increase. In sepsis, the contribution of Qha to maintain hepatic Do2 was reduced, which jeopardized hepatic V̇o2 further. Renal arterial flow was similarly affected by CVP increase as Qha.NEW & NOTEWORTHY Sepsis impairs intrinsic mechanisms to attenuate effects of increasing back pressure on hepatic oxygen transport.

The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial.

BACKGROUND: Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting. METHODS: In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [µg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4). RESULTS: Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] µg/kg/min in the DEX group and 0.04 [0.01, 0.16] µg/kg/min in the usual care group (p = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio. CONCLUSIONS: In critically ill patients with septic shock, patients in the DEX group received similar vasopressor doses in the first 48 h compared to the usual care group. On multivariable adjusted analysis, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target MAP. TRIAL REGISTRATION: The SPICE III trial was registered at ClinicalTrials.gov ( NCT01728558 ).

Bacteriophages Improve Outcomes in Experimental Staphylococcus aureus Ventilator-associated Pneumonia.

Rationale: Infections caused by multidrug-resistant bacteria are a major clinical challenge. Phage therapy is a promising alternative antibacterial strategy.Objectives: To evaluate the efficacy of intravenous phage therapy for the treatment of ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus in rats.Methods: In a randomized, blinded, controlled experimental study, we compared intravenous teicoplanin (3 mg/kg, n = 12), a cocktail of four phages (2-3 × 109 plaque-forming units/ml of 2003, 2002, 3A, and K; n = 12), and a combination of both (n = 11) given 2, 12, and 24 hours after induction of pneumonia, and then once daily for 4 days. The primary outcome was survival at Day 4. Secondary outcomes were bacterial and phage densities in lungs and spleen, histopathological scoring of infection within the lungs, and inflammatory biomarkers in blood.Measurements and Main Results: Treatment with either phages or teicoplanin increased survival from 0% to 58% and 50%, respectively (P < 0.005). The combination of phages and antibiotics did not further improve outcomes (45% survival). Animal survival correlated with reduced bacterial burdens in the lung (1.2 × 106 cfu/g of tissue for survivors vs. 1.2 × 109 cfu/g for nonsurviving animals; P < 0.0001), as well as improved histopathological outcomes. Phage multiplication within the lung occurred during treatment. IL-1ß increased in all treatment groups over the course of therapy.Conclusions: Phage therapy was as effective as teicoplanin in improving survival and decreasing bacterial load within the lungs of rats infected with methicillin-resistant S. aureus. Combining antibiotics with phage therapy did not further improve outcomes.

Fluid management in patients undergoing cardiac surgery: effects of an acetate- versus lactate-buffered balanced infusion solution on hemodynamic stability (HEMACETAT).

BACKGROUND: Recent evidence suggests that acetate-buffered infusions result in better hemodynamic stabilization than 0.9% saline in patients undergoing major surgery. The choice of buffer in balanced crystalloid solutions may modify their hemodynamic effects. We therefore compared the inopressor requirements of Ringer's acetate and lactate for perioperative fluid management in patients undergoing cardiac surgery. METHODS: Using a randomized controlled double-blind design, we compared Ringer's acetate (RA) to Ringer's lactate (RL) with respect to the average rate of inopressor administered until postoperative hemodynamic stabilization was achieved. Secondary outcomes were the cumulative dose of inopressors, the duration of inopressor administration, the total fluid volume administered, and the changes in acid-base homeostasis. Patients undergoing elective valvular cardiac surgery were included. Patients with severe cardiac, renal, or liver disease were excluded from the study. RESULTS: Seventy-five patients were randomly allocated to the RA arm, 73 to the RL. The hemodynamic profiles were comparable between the groups. The groups did not differ with respect to the average rate of inopressors (RA 2.1 mcg/kg/h, IQR 0.5-8.1 vs. RL 1.7 mcg/kg/h, IQR 0.7-8.2, p = 0.989). Cumulative doses of inopressors and time on individual and combined inopressors did not differ between the groups. No differences were found in acid-base parameters and their evolution over time. CONCLUSION: In this study, hemodynamic profiles of patients receiving Ringer's lactate and Ringer's acetate were comparable, and the evolution of acid-base parameters was similar. These study findings should be evaluated in larger, multi-center studies. TRIAL REGISTRATION: Clinicaltrials.gov NCT02895659 . Registered 16 September 2016.

Metabolic support in the critically ill: a consensus of 19.

Metabolic alterations in the critically ill have been studied for more than a century, but the heterogeneity of the critically ill patient population, the varying duration and severity of the acute phase of illness, and the many confounding factors have hindered progress in the field. These factors may explain why management of metabolic alterations and related conditions in critically ill patients has for many years been guided by recommendations based essentially on expert opinion. Over the last decade, a number of randomized controlled trials have been conducted, providing us with important population-level evidence that refutes several longstanding paradigms. However, between-patient variation means there is still substantial uncertainty when translating population-level evidence to individuals. A cornerstone of metabolic care is nutrition, for which there is a multifold of published guidelines that agree on many issues but disagree on others. Using a series of nine questions, we provide a review of the latest data in this field and a background to promote efforts to address the need for international consistency in recommendations related to the metabolic care of the critically ill patient. Our purpose is not to replace existing guidelines, but to comment on differences and add perspective.

Right atrial pressure and venous return during cardiopulmonary bypass.

The relevance of right atrial pressure (RAP) as the backpressure for venous return (QVR) and mean systemic filling pressure as upstream pressure is controversial during dynamic changes of circulation. To examine the immediate response of QVR (sum of caval vein flows) to changes in RAP and pump function, we used a closed-chest, central cannulation, heart bypass porcine preparation (n = 10) with venoarterial extracorporeal membrane oxygenation. Mean systemic filling pressure was determined by clamping extracorporeal membrane oxygenation tubing with open or closed arteriovenous shunt at euvolemia, volume expansion (9.75 ml/kg hydroxyethyl starch), and hypovolemia (bleeding 19.5 ml/kg after volume expansion). The responses of RAP and QVR were studied using variable pump speed at constant airway pressure (PAW) and constant pump speed at variable PAW Within each volume state, the immediate changes in QVR and RAP could be described with a single linear regression, regardless of whether RAP was altered by pump speed or PAW (r2 = 0.586-0.984). RAP was inversely proportional to pump speed from zero to maximum flow (r2 = 0.859-0.999). Changing PAW caused immediate, transient, directionally opposite changes in RAP and QVR (RAP: P ≤ 0.002 and QVR: P ≤ 0.001), where the initial response was proportional to the change in QVR driving pressure. Changes in PAW generated volume shifts into and out of the right atrium, but their effect on upstream pressure was negligible. Our findings support the concept that RAP acts as backpressure to QVR and that Guyton's model of circulatory equilibrium qualitatively predicts the dynamic response from changing RAP.NEW & NOTEWORTHY Venous return responds immediately to changes in right atrial pressure. Concomitant volume shifts within the systemic circulation due to an imbalance between cardiac output and venous return have negligible effects on mean systemic filling pressure. Guyton's model of circulatory equilibrium can qualitatively predict the resulting changes in dynamic conditions with right atrial pressure as backpressure to venous return.

Dysphagia in Mechanically Ventilated ICU Patients (DYnAMICS): A Prospective Observational Trial.

OBJECTIVES: Swallowing disorders may be associated with adverse clinical outcomes in patients following invasive mechanical ventilation. We investigated the incidence of dysphagia, its time course, and association with clinically relevant outcomes in extubated critically ill patients. DESIGN: Prospective observational trial with systematic dysphagia screening and follow-up until 90 days or death. SETTINGS: ICU of a tertiary care academic center. PATIENTS: One thousand three-hundred four admissions of mixed adult ICU patients (median age, 66.0 yr [interquartile range, 54.0-74.0]; Acute Physiology and Chronic Health Evaluation-II score, 19.0 [interquartile range, 14.0-24.0]) were screened for postextubation dysphagia. Primary ICU admissions (n = 933) were analyzed and followed up until 90 days or death. Patients from an independent academic center served as confirmatory cohort (n = 220). INTERVENTIONS: Bedside screening for dysphagia was performed within 3 hours after extubation by trained ICU nurses. Positive screening triggered confirmatory specialist bedside swallowing examinations and follow-up until hospital discharge. MEASUREMENTS AND MAIN RESULTS: Dysphagia screening was positive in 12.4% (n = 116/933) after extubation (18.3% of emergency and 4.9% of elective patients) and confirmed by specialists within 24 hours from positive screening in 87.3% (n = 96/110, n = 6 missing data). The dysphagia incidence at ICU discharge was 10.3% (n = 96/933) of which 60.4% (n = 58/96) remained positive until hospital discharge. Days on feeding tube, length of mechanical ventilation and ICU/hospital stay, and hospital mortality were higher in patients with dysphagia (all p < 0.001). The univariate hazard ratio for 90-day mortality for dysphagia was 3.74 (95% CI, 2.01-6.95; p < 0.001). After adjustment for disease severity and length of mechanical ventilation, dysphagia remained an independent predictor for 28-day and 90-day mortality (excess 90-d mortality 9.2%). CONCLUSIONS: Dysphagia after extubation was common in ICU patients, sustained until hospital discharge in the majority of affected patients, and was an independent predictor of death. Dysphagia after mechanical ventilation may be an overlooked problem. Studies on underlying causes and therapeutic interventions seem warranted.

A randomized controlled pilot study to evaluate the effect of an enteral formulation designed to improve gastrointestinal tolerance in the critically ill patient-the SPIRIT trial.

BACKGROUND: Diarrhea is frequent in patients in intensive care units (ICU) and is associated with discomfort and complications and may increase the length of stay and nursing workload. METHODS: This was a prospective, double-blind, randomized, controlled single-center pilot study to assess the incidence and frequency of diarrhea and the respective effects of a modified enteral diet (intervention: Peptamen® AF, rich in proteins, medium chain triglycerides and fish oil) compared to a standard diet (control: Isosource® Energy) in 90 randomized adult patients (intervention, n = 46; control, n = 44) with an ICU stay ≥5 days and tube feeding ≥3 days. Tube feeding was initiated within 72 h of ICU admission and continued up to 10 days. The caloric goal was adjusted to needs by indirect calorimetry. Gastrointestinal function, nutritional intake, and nursing workload were recorded. Follow-up was until 28 days after randomization. RESULTS: Median age was 63.3 (interquartile range (IQR) 51.0-73.2) years and Simplified Acute Physiology Score (SAPS) II was 61.0 (IQR 47.8-74). Time to reach caloric goal (intervention: 2.2 (0.8-3.7) days (median, IQR); control: 2.0 (1.3-2.7) days; p = 0.16), length of time on study nutrition (intervention: 5.0 (3.6-6.4) days; control: 7.0 (5.3-8.7) days; p = 0.26), and calorie intake (intervention: 18.0 (12.5-20.9) kcal/kg/day; control 19.7 (17.3-23.1) kcal/kg/day; p = 0.08) did not differ between groups, with a higher protein intake for Peptamen® group (1.13 (0.78-1.31) g/kg/day vs 0.80 (0.70-0.94); p < 0.001). No difference in diarrhea incidence (intervention group: 29 (64%); control group: 31 (70%); p = 0.652), use of fecal collectors (23 (51%) vs. 24 (55%); p = 0.83), or diarrhea-free days (161 (64%) vs 196 (68%); p = 0.65) was found. Nursing workload and cost for diarrhea care were not different between the groups. In a post-hoc analysis, adjusted for treatment group, age, sex, and SAPS II score, diarrhea was associated with length of mechanical ventilation (9.5 (6.0-13.1) vs. 3.9 (3.2-4.6) days; p = 0.006) and length of ICU stay (11.0 (8.9-13.1) vs. 5.0 (3.8-6.2) days; p = 0.001). CONCLUSIONS: In this pilot study, we found a high incidence of diarrhea, which was not attenuated by Peptamen® AF. Patients with diarrhea stayed longer in the ICU. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01581957 . Registered on 18 April 2012.

Time course of blood lactate levels, inflammation, and mitochondrial function in experimental sepsis.

BACKGROUND: A decrease in blood lactate levels (Lac) >10% during the first hours of resuscitation in sepsis is associated with better outcomes, but the mechanisms are unclear. Our objective was to investigate the relationship between the time course of Lac, inflammatory response, and mitochondrial respiration during experimental sepsis. METHODS: Original data from two previously published studies were reanalyzed. In cohort 1, pigs were randomized to be resuscitated for 48 h starting at 6, 12, and 24 h, respectively, after fecal peritonitis induction (n = 8 each). Animals were categorized according to the decrease in Lac during the first 6 h of resuscitation (early if ≥10% [Lac ≥10%] or late if <10% or increased [Lac <10%]), and systemic hemodynamics, inflammatory parameters, and mitochondrial function were compared between groups. In a second group of animals with fecal peritonitis and 24 h of resuscitation (n = 16, cohort 2), abdominal regional Lac exchange was measured, and animals were categorized according to the decrease in Lac as in cohort 1. RESULTS: Overall mortality was 20% (4 of 20) in the Lac ≥10% group and 60% (12 of 20) in the Lac <10% group (p = 0.022). In cohort 1, systemic hemodynamics were similar in the Lac ≥10% (n = 13) and Lac <10% (n = 11) groups. Plasma interleukin-6 levels increased during unresuscitated sepsis and decreased during resusciation in both groups, but they were lower at study end in the Lac ≥10% group (p = 0.047). Complexes I and II maximal (state 3) and resting (state 4) isolated brain mitochondrial respiration at study end was higher in the Lac ≥10% group than in the Lac <10% group, whereas hepatic, myocardial, and skeletal muscle mitochondrial respiration was similar in both groups. In cohort 2, mesenteric, total hepatic, and renal blood flow at study end was higher in the Lac ≥10% group (n = 7) than in the Lac <10% group (n = 9), despite similar cardiac output. Hepatic lactate influx and uptake in the Lac ≥10% group were approximately 1.5 and 3 times higher, respectively, than in the Lac <10% group (p = 0.066 for both). CONCLUSIONS: A decrease in Lac >10% during early resuscitation (6 h) after abdominal sepsis is associated with lower levels of plasma interleukin-6 and improved brain but not hepatic or muscle mitochondrial respiration. Blood flow redistribution to abdominal organs in animals with early decrease in Lac concentrations increases the potential to both deliver and extract Lac.

Estimation of the global burden of mesothelioma deaths from incomplete national mortality data.

BACKGROUND: Mesothelioma is increasingly recognised as a global health issue and the assessment of its global burden is warranted. OBJECTIVES: To descriptively analyse national mortality data and to use reported and estimated data to calculate the global burden of mesothelioma deaths. METHODS: For the study period of 1994 to 2014, we grouped 230 countries into 59 countries with quality mesothelioma mortality data suitable to be used for reference rates, 45 countries with poor quality data and 126 countries with no data, based on the availability of data in the WHO Mortality Database. To estimate global deaths, we extrapolated the gender-specific and age-specific mortality rates of the countries with quality data to all other countries. RESULTS: The global numbers and rates of mesothelioma deaths have increased over time. The 59 countries with quality data recorded 15 011 mesothelioma deaths per year over the 3 most recent years with available data (equivalent to 9.9 deaths per million per year). From these reference data, we extrapolated the global mesothelioma deaths to be 38 400 per year, based on extrapolations for asbestos use. CONCLUSIONS: Although the validity of our extrapolation method depends on the adequate identification of quality mesothelioma data and appropriate adjustment for other variables, our estimates can be updated, refined and verified because they are based on commonly accessible data and are derived using a straightforward algorithm. Our estimates are within the range of previously reported values but higher than the most recently reported values.