Background

Local formation of nitric oxide (NO) in the lung in proportion to ventilation, leading to vasodilation, is a putative mechanism behind ventilation- perfusion matching. We examined the role of local constitutive NO formation on regional distributions of ventilation (V) and perfusion (Q) and ventilation-perfusion matching (V/Q) in mechanically ventilated adult sheep with normal gas exchange.

Methods

V and Q were analyzed in lung regions (≈1.5 cm3) before and after inhibition of constitutive nitric oxide synthase (cNOS) with Nω-nitro-L-arginine methyl ester (L-NAME) (25 mg/kg) in seven prone sheep ventilated with PEEP. V and Q were measured using aerosolized fluorescent and infused radiolabeled microspheres, respectively. The animals were exsanguinated while deeply anaesthetized; lungs were excised, dried at total lung capacity and divided into cube units. The spatial location for each cube was tracked and fluorescence and radioactivity per unit weight determined.

Results

Pulmonary artery pressure increased significantly after L-NAME (from mean 16.6 to 23.6 mmHg, P<0.01) while there were no significant changes in PaO2, PaCO2 or SD log(V/Q). Distribution of V was not influenced by L-NAME but a small redistribution of Q from ventral to dorsal lung regions resulting in less heterogeneity in Q along the gravitational axis was seen (p<0.01). Perfusion to regions with the highest ventilation (5th quintile of the V distribution) remained unchanged with L-NAME.

Conclusions

There was minimal or no influence of cNOS inhibition by L-NAME on the distributions of V and Q, and V/Q in prone anesthetized and ventilated adult sheep with normal gas exchange.

Introduction: Cardiac dysfunction is a well-known complication of sepsis, but its long-term consequences remain unclear. The aim of this study was to investigate cardiac outcome after sepsis by assessing causes of death in a nationwide register-based cohort.

Methods: A cohort of 9,520 severe sepsis and septic shock intensive care (ICU) patients without preceding severe cardiac failure and discharged alive from the ICU was collected from the Swedish Intensive Care Registry (SIR) from 2008 to 2013, together with a nonseptic control group (n = 4,577). Patients were matched according to age, sex and severity of illness. Information on cause of death after ICU discharge was sought in the Swedish National Board of Health and Welfare’s Cause of Death Registry.

Results: After ICU discharge, 3,954 (42%) of severe sepsis or septic shock patients died. In 654 (16%) of these, cardiac failure was registered as the cause of death. The follow-up time was 17,693 person-years (median 583 days/person; maximum 5.7 years) and the median (IQR) time from ICU discharge to cardiac failure-related death 81 (17 - 379) days. With increasing severity of illness (quartiles of SAPS3), the hazard rate for cardiac failure-related death increased (hazard ratio (HR) 1.58 (95% CI 1.19 - 2.09, p <0.001) in the highest quartile compared to the lowest). In a matched comparison between severe sepsis or septic shock patients and controls, survival was similar, and the hazard rate for cardiac failurerelated death did not differ between groups (HR 0.97, 95% CI 0.88 – 1.10, p = 0.62).

Conclusions: The risk of death with cardiac failure as the cause of death after severe sepsis or septic shock increases with severity of illness on admission. Patients with severe sepsis or septic shock are not, however, at an increased risk of death with cardiac failure as the cause of death when compared to other ICU patients with similar severity of illness.

Introduction: Acute Kidney Injury (AKI) is common in critical ill populations and its association with high short-term mortality is well established. However, long-term risks of death and renal dysfunction are poorly understood and few studies exclude patients with pre-existing renal disease, meaning outcome for de novo AKI has been difficult to elicit. We aimed to compare the long-term risk of Chronic Kidney Disease (CKD), End Stage Renal Disease (ESRD) and mortality in critically ill patients with and without severe de novo AKI. Method: This cohort study was conducted between 2005 and 2011 in Swedish intensive care units (ICU). Data from 130134 adult patients listed on the Swedish intensive care register-database was linked with other national registries. Patients with pre-existing CKD (4192) and ESRD (1389) were excluded, as were cases (26771) with incomplete data. Patients were classified according to AKI exposure during ICU admission. Outcome in the de novo AKI group was compared to the non-exposed (no-AKI) intensive care control group. Primary outcome was all-cause mortality. Follow-up ranged from one to seven years (median 2.1 years). Secondary outcomes were incidence of CKD and ESRD and median follow-up was 1.3 years. Results: Of 97 782 patients, 5273 (5.4%) had de novo AKI. These patients had significantly higher crude mortality at one (48.4% vs. 24.6%) and five years (61.8% vs. 39.1%) compared to the control group. The first 30% of deaths in AKI patients occurred within 11 days of ICU admission whilst the 30-centile in the no-AKI group died by 748 days. CKD was significantly more common in AKI survivors at one year (6.0% vs. 0.44%) than in no-AKI group (adjusted incidence rate ratio (IRR) 7.6). AKI patients also had significantly higher rates of ESRD at one (2.0% vs. 0.08%) and at five years (3.9% vs. 0.3%) than those in the comparison group (adjusted IRR 22.5). Conclusion: This large cohort study demonstrated that de novo AKI is associated with increased short and long-term risk of death. AKI is independently associated with increased risk of CKD and ESRD as compared to an ICU control population. Severe de novo AKI survivors should be routinely followed-up and their renal function monitored.

Introduction: Preclinical data indicate that oestrogen appears to play a beneficial role in the pathophysiology of and recovery from critical illness. In few previous epidemiologic studies, however, have researchers analysed premenopausal women as a separate group when addressing potential gender differences in critical care outcome. Our aim was to see if women of premenopausal age have a better outcome following critical care and to investigate the association between gender and use of intensive care unit (ICU) resources. Methods: On the basis of our analysis of 127,254 consecutive Simplified Acute Physiology Score III-scored Swedish Intensive Care Registry ICU admissions from 2008 through 2012, we determined the risk-adjusted 30-day mortality, accumulated nurse workload score and ICU length of stay. To investigate associations with sex, we used logistic regression and multivariate analyses on the entire cohort as well as on two subgroups stratified by median age for menopause (up to and including 45 years and older than 45 years) and six selected diagnostic subgroups (sepsis, multiple trauma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, pneumonia and cardiac arrest). Results: There was no sex difference in risk-adjusted mortality for the cohort as a whole, and there was no sex difference in risk-adjusted mortality in the group 45 years of age and younger. For the group of patients older than 45 years of age, we found a reduced risk-adjusted mortality in men admitted for cardiac arrest. For the cohort as a whole, and for those admitted with multiple trauma, male sex was associated with a higher nurse workload score and a longer ICU stay. Conclusions: Using information derived from a large multiple ICU register database, we found that premenopausal female sex was not associated with a survival advantage following intensive care in Sweden. When the data were adjusted for age and severity of illness, we found that men used more ICU resources per admission than women did.

Introduction

The development of intensive care medicine has led to improved survival of patients with complex illnesses and extensive injuries. Survivors are at risk of acquiring physical and functional deficits that may have negative effects on health-related quality of life (HRQoL). The significance of measuring HRQoL has been underlined by critical care researchers since poor HRQoL is associated with an adverse prognosis.

Objective

The aim of this work was to examine the development of HRQoL at 2, 6 and 12 months after ICU discharge in a mixed ICU patient population with an ICU-stay > 96 hrs.

Methods

We analysed admissions during 2008-2014 to 49 ICUs that submitted follow-up data to the Swedish Intensive Care Registry (SIR, http://www.icuregswe.org). HRQoL was measured using the Short Form 36 (SF36) questionnaire at 2, 6, and 12 months after discharge from ICU. SF36 domains, age, gender, illness severity on admission (SAPS3 probabilities) and length of ICU-stay were analysed for the entire cohort and for important diagnostic groups. SF36 scores were compared to an age- and gender-adjusted Swedish normal population. Differences in SF36 domains were analysed using non-parametric methods. Medians and interquartile ranges are presented.

Results

Complete SF36 responses were analysed for 4453, 4019 and 2515 admissions at 2, 6 and 12 months, respectively. HRQoL at 2 months in patients that subsequently were lost to follow-up was generally similar to those with follow-up, but they were younger, less ill and had shorter ICU-stay. Full longitudinal data with complete SF36 responses were obtained in 1438 patients [Age: 66 yrs. (57-73 yrs.), female gender: 37.2%, SAPS3 prob: 0.36 (0.19-0.55), ICU-stay: 7.0 days (4.9-11.5 days)]. SF36 improved over time in all domains (P < 0.001, Table), although some domains remained stable from 6 to 12 months. Patterns of recovery differed between important diagnostic groups (i.e. sepsis, out-of-hospital cardiac arrest, COPD, ARDS). A large proportion of patients (10-25% depending on SF36 domain) had HRQoL scores at 12 months which was below 2 standard deviations of the age- and gender-adjusted Swedish norm. The cardiac arrest group were among those with best, and the COPD group were among those with worst HRQoL at 12 months.

Conclusions

HRQoL recovered over 12 months in critically ill patients with a prolonged ICU stay. Recovery varied between diagnostic groups and a large proportion of patients had markedly depressed HRQoL. These findings may have important implications for follow-up and care after critical illness.

Background: Standardised mortality ratio (SMR) is a common quality indicator in critical care and is the ratio between observed mortality and expected mortality. Typically, in-hospital mortality is used to derive SMR, but the use of a time-fixed, more objective, endpoint has been advocated. This study aimed to determine the relationship between in-hospital mortality and 30-day mortality on a comprehensive Swedish intensive care cohort.

Methods: A retrospective study on patients >15 years-old, from the Swedish Intensive Care Register (SIR), where intensive care unit (ICU) admissions in 2009-2010 were matched with the corresponding hospital admissions in the Swedish Hospital Discharge Register. Recalibrated SAPS (Simplified Acute Physiology Score) 3 models were developed to predict and compare in-hospital and 30-day mortality. SMR based on in-hospital mortality and on 30-day mortality were compared between ICUs and between groups with different case-mixes, discharge destinations and length of hospital stays.

Results: Sixty-five ICUs with 48861 patients, of which 35610 were SAPS 3 scored, were included. Thirty-day mortality (17%) was higher than in-hospital mortality (14%). The SMR based on 30-day mortality and that based on in-hospital mortality differed significantly in 7/53 ICUs, for patients with sepsis, for elective surgery-admissions and in groups categorised according to discharge destination and hospital length of stay.

Conclusion: Choice of mortality end-point influences SMR. The extent of the influence depends on hospital-, ICU- and patient cohort characteristics as well as inter-hospital transfer rates, since all these factors influence the difference between SMR based on 30-day mortality and SMR based on in-hospital mortality.