Smoking is associated with higher risk of contracting bacterial infection and pneumonia, intensive care unit admission and death.

BACKGROUND: Smoking has been associated with a higher risk of contracting pneumonia, but contradictory results have shown that smoking may or may not decrease the risk of dying in pneumonia. The aim of this study is to investigate how smoking is associated with contracting any infection and pneumonia and death. METHOD AND FINDINGS: Participants were drawn from the population-based Cohort of Swedish Men and the Swedish Mammography Cohort, which are representative of the Swedish population. Participants have answered detailed lifestyle questionnaires and have been followed in national registers, such as the Patient Register, Cause of Death register and Swedish Intensive Care Registry. The risks of contracting infection and pneumonia or dying in infection and pneumonia were assessed using Cox regression. Of 62,902 cohort participants, 25,297 contracted an infection of which 4,505 died; and 10,471 contracted pneumonia of which 2,851 died. Compared to never smokers, former smokers at baseline had hazard ratio (HR) 1.08 (95% confidence interval (CI) 1.05-1.12) of contracting and HR 1.19 (95% CI 1.11-1.28) of dying in infection and HR 1.17 (95% CI 1.12-1.23) of contracting and HR 1.16 (95% CI 1.06-1.27) of dying in pneumonia during follow-up. Compared to never smokers, current smokers at baseline had HR 1.17 (95% CI 1.13-1.21) of contracting infection and HR 1.64 (95% CI 1.52-1.77) dying in infection; HR 1.42 (95% CI 1.35-1.49) of contracting pneumonia and HR 1.70 (95% CI 1.55-1.87) of dying in pneumonia during follow-up. The risk of contracting and dying in infection and pneumonia increased in a dose-response manner with number of pack years smoked and decreased with years since smoking cessation. CONCLUSION: Smoking is associated with contracting and dying in any infection and pneumonia and the risk increases with pack years smoked, highlighting the importance of both primary prevention and smoking cessation.

Physical activity is associated with a lower risk of contracting and dying in infection and sepsis: a Swedish population-based cohort study.

BACKGROUND: Sepsis is a condition where the immune response to infection becomes dysregulated and life-threatening. It is not known whether lifestyle factors influence the risk of sepsis. The aim of the present study is to investigate the association between physical activity and the risk of acquiring and dying in infection or sepsis. METHODS: The population-based Swedish Mammography Cohort and Cohort of Swedish Men sent participants lifestyle questionnaires in 1997 and have subsequently followed participants in national Swedish registers, including the National Patient Register, the Swedish Intensive Care Registry and the Cause of Death Register. The risk of contracting infection and sepsis, the risk of intensive care unit admission and the risk of death were estimated using multivariable Cox regression. RESULTS: Among 64,850 cohort participants, 26,124 individuals suffered at least one episode of infection or sepsis and 4708 individuals died of infection or sepsis during the study period. In adjusted analyses, compared to exercising less than one hour per week, stated exercise one hour per week was associated with lower risk of contracting infection or sepsis, hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.90-0.97), and lower risk of dying in infection or sepsis, HR 0.87 (95% CI 0.80-0.96). Further exercise was associated with even lower risk, and similar patterns were observed for walking. The population-attributable risks of contracting and dying in infection or sepsis for not exercising were 2.6% and 4.5%, respectively. CONCLUSIONS: Exercise and walking demonstrate inverse dose-response associations with both the risk of contracting and dying in infection and sepsis, presenting possible preventative interventions for this critical condition.

Prior physical illness predicts death better than acute physiological derangement on intensive care unit admission in COVID-19: A Swedish registry study.

COVID-19 is associated with prolonged intensive care unit (ICU) stay and considerable mortality. The onset of persistent critical illness, defined as when prior illness predicts death better than acute physiological derangement, has not been studied in COVID-19. This national cohort study based on the Swedish Intensive Care Registry (SIR) included all patients admitted to a Swedish ICU due to COVID-19 from 6 March 2020 to 9 November 2021. Simplified Acute Physiology Score-3 (SAPS3) Box 1 was used as a measure of prior illness and Box 3 as a measure of acute derangement to evaluate the onset and importance of persistent critical illness in COVID-19. To compare predictive capacity, the area under receiver operating characteristic (AUC) of SAPS3 and its constituent Box 1 and 3 was calculated for 30-day mortality. In 7 969 patients, of which 1 878 (23.6%) died within 30 days of ICU admission, the complete SAPS3 score had acceptable discrimination: AUC 0.75 (95% CI 0.74 to 0.76) but showed under prediction in low-risk patients and over prediction in high-risk patients. SAPS3 Box 1 showed markedly better discrimination than Box 3 (AUC 0.74 vs 0.65, P<0,0001). Using custom logistic models, the difference in predictive performance of prior and acute illness was validated, AUC 0.76 vs AUC 0.69, p<0.0001. Prior physical illness predicts death in COVID-19 better than acute physiological derangement during ICU stay, and the whole SAPS3 score is not significantly better than just prior illness. The results suggests that COVID-19 may exhibit similarities to persistent critical illness immediately from ICU admission, potentially because of long median ICU length-of-stay. Alternatively, the variables in the acute physiological derangement model may not adequately capture the severity of illness in COVID-19.

Strain on the ICU resources and patient outcomes in the COVID-19 pandemic: A Swedish national registry cohort study.

BACKGROUND: The Coronavirus 2019 (COVID-19) pandemic has led to an unprecedented strain on the ICU resources. It is not known how the ICU resources employed in treating COVID-19 patients are related to inpatient characteristics, use of organ support or mortality. OBJECTIVES: To investigate how the use of ICU resources relate to use of organ support and mortality in COVID-19 patients. DESIGN: A national register-based cohort study. SETTING: All Swedish ICUs from March 2020 to November 2021. PATIENTS: All patients admitted to Swedish ICUs with a primary diagnosis of COVID-19 reported to the national Swedish Intensive Care Register (SIR). MAIN OUTCOME MEASURES: Organ support (mechanical ventilation, noninvasive ventilation, high-flow oxygen therapy, prone positioning, surgical and percutaneous tracheostomy, central venous catheterisation, continuous renal replacement therapy and intermittent haemodialysis), discharge at night, re-admission, transfer and ICU and 30-day mortality. RESULTS: Seven thousand nine hundred and sixty-nine patients had a median age of 63 years, and 70% were men. Median daily census was 167% of habitual census, daily new admissions were 20% of habitual census and the median occupancy was 82%. Census and new admissions were associated with mechanical ventilation, OR 1.37 (95% CI 1.28 to 1.48) and OR 1.44 (95% CI 1.13 to 1.84), respectively, but negatively associated with noninvasive ventilation, OR 0.83 (95% CI 0.77 to 0.89) and OR 0.40 (95% CI 0.30 to 52) and high-flow oxygen therapy, OR 0.72 (95% CI 0.67 to 0.77) and OR 0.77 (95% CI 0.61 to 0.97). Occupancy above 90% of available beds was not associated with mechanical ventilation or noninvasive ventilation, but with high-flow oxygen therapy, OR 1.36 (95% CI 1.21 to 1.53). All measures of pressure on resources were associated with transfer to other hospitals, but none were associated with discharge at night, ICU mortality or 30-day mortality. CONCLUSIONS: Pressure on ICU resources was associated with more invasive respiratory support, indicating that during these times, ICU resources were reserved for sicker patients.

The Contribution of Plasma Urea to Total Osmolality During Iatrogenic Fluid Reduction in Critically Ill Patients.

Hyperosmolality is common in critically ill patients during body fluid volume reduction. It is unknown whether this is only a result of decreased total body water or an active osmole-producing mechanism similar to that found in aestivating animals, where muscle degradation increases urea levels to preserve water. We hypothesized that fluid volume reduction in critically ill patients contributes to a shift from ionic to organic osmolytes similar to mechanisms of aestivation. We performed a post-hoc analysis on data from a multicenter observational study in adult intensive care unit (ICU) patients in the postresuscitative phase. Fluid, electrolyte, energy and nitrogen intake, fluid loss, estimated glomerular filtration rate (eGFR), and estimated plasma osmolality (eOSM) were registered. Contributions of osmolytes Na+, K+, urea, and glucose to eOSM expressed as proportions of eOSM were calculated. A total of 241 patients were included. eOSM increased (median change 7.4 mOsm/kg [IQR-1.9-18]) during the study. Sodium's and potassium's proportions of eOSM decreased (P < .05 and P < .01, respectively), whereas urea's proportion increased (P < .001). The urea's proportion of eOSM was higher in patients with negative vs. positive fluid balance. Urea's proportion of eOSM increased with eOSM (r = 0.63; adjusted for eGFR r = 0.80), but not nitrogen intake. In patients without furosemide and/or renal replacement therapy (n = 17), urea's proportion of eOSM and eOSM correlated strongly (r = 0.92). Urea's proportion of eOSM was higher in patients not surviving up to 90 d. In stabilized ICU patients, the contribution of urea to plasma osmolality increased during body water volume reduction, statistically independently of nitrogen administration and eGFR. The shift from ionic osmolytes to urea during body fluid volume reduction is similar to that seen in aestivating animals. ClinicalTrials.org Identifier: NCT03972475.

Hidden sources of fluids, sodium and potassium in stabilised Swedish ICU patients: A multicentre retrospective observational study.

BACKGROUND: Fluid overload in ICU patients is associated with increased morbidity and mortality. Although studies report on optimisation of resuscitation fluids given to ICU patients, increasing evidence suggests that maintenance fluids and fluids used to administer drugs are important sources of fluid overload. OBJECTIVES: We aimed to evaluate the volume of maintenance fluids and electrolytes on overall fluid balance and their relation to mortality in stabilised ICU patients. DESIGN: Multicentre retrospective observational study. SETTING: Six mixed surgical and medical ICUs in Sweden. PATIENTS: A total of 241 adult patients who spent at least 7 days in the ICU during 2018. MAIN OUTCOME MEASURES: The primary endpoint was the volume of maintenance, resuscitation and drug diluent fluids administered on days 3 to 7 in the ICU. Secondary endpoints were to compare dispensed amounts of maintenance fluids and electrolytes with predicted requirements. We also investigated the effects of administered fluids and electrolytes on patient outcomes. RESULTS: During ICU days 3 to 7, 56.4% of the total fluids given were maintenance fluids, nutritional fluids or both, 25.4% were drug fluids and 18.1% were resuscitation fluids. Patients received fluids 1.29 (95% confidence interval 1.07 to 1.56) times their estimated fluid needs. Despite this, 93% of the cohort was treated with diuretics or renal replacement therapy. Patients were given 2.17 (1.57 to 2.96) times their theoretical sodium needs and 1.22 (0.75 to 1.77) times their potassium needs. The median [IQR] volume of fluid loss during the 5-day study period was 3742 [3156 to 4479] ml day-1, with urine output the main source of fluid loss. Death at 90 days was not associated with fluid or electrolyte balance in this cohort. CONCLUSION: Maintenance and drug fluids far exceeded resuscitative fluids in ICU patients beyond the resuscitative phase. This excess fluid intake, in conjunction with high urinary output and treatment for fluid offload in almost all patients, suggests that a large volume of the maintenance fluids given was unnecessary. TRIAL REGISTRATION: ClinicalTrials.org NCT03972475.

Endotoxin Removal in Septic Shock with the Alteco LPS Adsorber Was Safe But Showed no Benefit Compared to Placebo in the Double-Blind Randomized Controlled Trial-the Asset Study.

PURPOSE: Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco LPS Adsorber for LPS removal in early gram-negative septic shock was feasible and safe. Also, effects on endotoxin level, inflammatory response, and organ function were assessed. METHODS: A pilot, double-blinded, randomized, Phase IIa, feasibility clinical investigation was undertaken in six Scandinavian intensive care units aiming to allocate 32 septic shock patients with abdominal or urogenital focus on LPS Adsorber therapy or a Sham Adsorber, therapy without active LPS binding. The study treatment was initiated within 12 h of inclusion and given for 6 h daily on first 2 days. LPS was measured in all patients. RESULTS: The investigation was terminated after 527 days with eight patients included in the LPS Adsorber group and seven in the Sham group. Twenty-one adverse effects, judged not to be related to the device, were reported in three patients in the LPS Adsorber group and two in the Sham group. Two patients in the Sham group and no patients in the LPS Adsorber group died within 28 days. Plasma LPS levels were low without groups differences during or after adsorber therapy. The changes in inflammatory markers and organ function were similar in the groups. CONCLUSIONS: In a small cohort of patients with presumed gram-negative septic shock, levels of circulating endotoxin were low and no adverse effects within 28 days after LPS adsorber-treatment were observed. No benefit compared with a sham device was seen when using a LPS adsorber in addition to standard care. TRIAL REGISTRATION: Clinicaltrials.gov NCT02335723. Registered: November 28, 2014.

Abdominal Septic Shock - Endotoxin Adsorption Treatment (ASSET) - endotoxin removal in abdominal and urogenital septic shock with the Alteco® LPS Adsorber: study protocol for a double-blinded, randomized placebo-controlled trial.

BACKGROUND: Severe sepsis and septic shock are common in intensive care and carry high mortality rates. In patients with Gram-negative infections, early and extensive removal of endotoxin may limit the inflammatory response that characterizes septic shock. The Alteco® LPS Adsorber (hereafter referred to cited as the lipopolysaccharide (LPS) Adsorber) can be used for endotoxin removal and attenuate the deleterious inflammatory and clinical responses seen in septic shock. METHODS/DESIGN: The Abdominal Septic Shock - Endotoxin Adsorption Treatment (ASSET) trial is a pilot study investigating the feasibility and safety of LPS Adsorber therapy. This pilot, multicenter, stratified, parallel, double-blinded, randomized, phase IIa, feasibility clinical investigation will be performed in five Scandinavian intensive care units. Thirty-two subjects with early septic shock and organ failure, following adequate resuscitation, will be randomized to receive either: extracorporeal veno-venous hemoperfusion therapy with the LPS Adsorber or veno-venous hemoperfusion therapy with a placebo adsorber (without active LPS-binding peptide). Patients will be stratified by infection focus such that 20 subjects with an abdominal focus (stratum A) and 12 subjects with a urogenital focus (stratum B) will be included in a parallel design. Thereafter, an interim analysis will be performed and an additional 12 patients may be included in the study. The study is designed as adaptive a priori: the patients from this study can be included in a later phase IIb study. The aim of the study is to investigate the feasibility of LPS Adsorber therapy commenced early in the time-course of septic shock. The primary endpoint will be a characterization of all reported unanticipated serious adverse device effects and anticipated serious adverse device effects. Secondary outcomes are decrease in endotoxin plasma concentration, impact on clinical outcome measures and impact on inflammatory response by LPS Adsorber therapy, as well as detailed description of the relevant mediators bound to the LPS Adsorber. Recruitment of patients will start in September 2015. DISCUSSION: The ASSET trial will give insight into the feasibility and safety of this LPS Adsorber therapy and preliminary data on its potential clinical effects in septic shock. Moreover, this pilot trial will provide with necessary data for designing future studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02335723 . Registered on 28 November 2014.

Brain death due to fat embolism - could moderate hypercapnia and prone position be blamed for the tonsillar herniation?

Fat embolism to the systemic circulation in polytrauma patients is very common. The fat embolism syndrome (FES), however, is a rare condition. We describe a case of traumatic femur fracture with FES that was presented as acute tonsillar herniation (coning) and brain death postoperatively. We believe that in this case the prone position and moderate hypercapnia contributed to the acute coning.

Spontaneous breathing improves shunt fraction and oxygenation in comparison with controlled ventilation at a similar amount of lung collapse.

BACKGROUND: Spontaneous breathing (SB), when allowed during mechanical ventilation (MV), improves oxygenation in different models of acute lung injury. However, it is not known whether oxygenation is improved during mechanically unsupported SB. Therefore, we compared SB without any support with controlled MV at identical tidal volume (VT) and respiratory rate (RR) without positive end-expiratory pressure in a porcine lung collapse model. METHODS: In 25 anesthetized piglets, stable lung collapse was induced by application of negative pressure, and animals were randomized to either resume SB or to be kept on MV at identical VT (5 mL/kg; 95% confidence interval: 3.8 to 6.4) and RR (65 per minute [57 to 73]) as had been measured during an initial SB period. Oxygenation was assessed by blood gas analysis (n=15) completed by multiple inert gas elimination technique (n=8 of the 15) for shunt measurement. In addition, possible lung recruitment was studied with computed tomography of the chest (n=10). RESULTS: After induction of lung collapse, PaO2/FIO2 decreased to 90 mm Hg (76 to 103). With SB, PaO2/FIO2 increased to 235 mm Hg (177 to 293) within 15 minutes, whereas MV at identical Vt and RR did not cause any improvement in oxygenation. Intrapulmonary shunt by 45 minutes after induction of lung collapse was lower during SB (SB: 27% [24 to 30] versus MV: 41% [28 to 55]; P=0.017). Neither SB nor MV reduced collapsed lung areas on computed tomography. CONCLUSIONS: SB without any support improves oxygenation and reduces shunt in comparison with MV at identical settings. This seems to be achieved without any major signs of recruitment of collapsed lung regions.

Analysis of dynamic intratidal compliance in a lung collapse model.

BACKGROUND: For mechanical ventilation to be lung-protective, an accepted suggestion is to place the tidal volume (V(T)) between the lower and upper inflection point of the airway pressure-volume relation. The drawback of this approach is, however, that the pressure-volume relation is assessed under quasistatic, no-flow conditions, which the lungs never experience during ventilation. Intratidal nonlinearity must be assessed under real (i.e., dynamic) conditions. With the dynamic gliding-SLICE technique that generates a high-resolution description of intratidal mechanics, the current study analyzed the profile of the compliance of the respiratory system (C(RS)). METHODS: In 12 anesthetized piglets with lung collapse, the pressure-volume relation was acquired at different levels of positive end-expiratory pressure (PEEP: 0, 5, 10, and 15 cm H(2)O). Lung collapse was assessed by computed tomography and the intratidal course of C(RS) using the gliding-SLICE method. RESULTS: Depending on PEEP, C(RS) showed characteristic profiles. With low PEEP, C(RS) increased up to 20% above the compliance at early inspiration, suggesting intratidal recruitment; whereas a profile of decreasing C(RS), signaling overdistension, occurred with V(T) > 5 ml/kg and high PEEP levels. At the highest volume range, C(RS) was up to 60% less than the maximum. With PEEP 10 cm H(2)O, C(RS) was high and did not decrease before 5 ml/kg V(T) was delivered. CONCLUSIONS: The profile of dynamic C(RS) reflects nonlinear intratidal mechanics of the respiratory system. The SLICE analysis has the potential to detect intratidal recruitment and overdistension. This might help in finding a combination of PEEP and V(T) level that is protective from a lung-mechanics perspective.

Change in expiratory flow detects partial endotracheal tube obstruction in pressure-controlled ventilation.

Only extreme degrees of endotracheal tube (ETT) narrowing can be detected with monitoring of tidal volume (V(T)) during pressure-controlled ventilation (PCV). To assess the degree of ETT obstruction in PCV and to compare it to V(T) monitoring, we produced 3 levels of partial ETT obstruction in 11 healthy anesthetized piglets using ETTs of 4 different inner diameters (IDs 9.0, 8.0, 7.0, and 6.0 mm). An expiratory flow over volume ((e)-V) curve was plotted and the time constant (tau(e)) at 15% of expiration time (T(e)) was calculated. We also calculated the fractional volume expired during the first 15% of T(e) (V(ex fract,15)) and compared those variables to full expiratory V(T) for each of the 3 obstructions. V(T) monitoring failed to detect ETT narrowing. By contrast, V(ex fract,15) decreased and tau(e) increased significantly with increasing ETT narrowing (for IDs 9.0, 8.0, 7.0, and 6.0, mean V(ex fract,15) was 195, 180, 146, and 134 mL respectively and mean tau(e) was 380, 491, 635, 794 ms for IDs 9.0, 8.0, 7.0, and 6.0 respectively). We conclude that when the elastic recoil that drives (e) is appropriately considered, analysis of (e) and V(ex fract,15) detects partial ETT obstruction during PCV.

Peak airway pressure increase is a late warning sign of partial endotracheal tube obstruction whereas change in expiratory flow is an early warning sign.

If peak inspiratory airway pressure (Ppeak) is used to monitor airway patency, progressive obstruction of the endotracheal tube (ETT) resulting from secretions can go undetected for a prolonged period. The reason is that any increase in Ppeak depends not only on the degree of narrowing but also on the inspiratory flow () rate. Although the impact of narrowing on low inspiratory is small, its decelerating effect on the high expiratory is pronounced and, hence, easily detectable. Dividing the volume-flow curve of a passive expiration into five consecutive segments (slices) and calculating the time constants (tau(Epsilon)) of these slices allows for analyzing whether and how expiratory is impeded by a partial obstruction. In nine piglets, during volume-controlled ventilation, three grades of ETT obstruction were created with an external clamp. In all animals the tau(E) increased with ETT obstruction (mean for the first slice: 550 ms with unobstructed ETT; grade 1: 661; grade 2: 877; and grade 3: 1563 ms, respectively) and this increase was significant with grade 2 and 3 obstruction. Ppeak, by contrast, did not increase significantly (base: 13, grade 1: 14, grade 2: 15 cm H(2)O) until the most severe (grade 3: 20 cm H(2)O) obstruction was created. We conclude that partial obstruction of the ETT can be reliably monitored with the expiratory V signal and has the potential of monitoring ETT narrowing in ventilator-dependent patients independent of the inspiratory pattern applied.

Decreasing size of cardiogenic oscillations reflects decreasing compliance of the respiratory system during long-term ventilation.

Part of the energy produced by the heartbeat is transferred to the lung and promotes intrapulmonary gas mixing. It is likely that this transmission in the form of local mechanical disturbances affects and reflects respiratory mechanics. The effects of the cardiogenic oscillations were studied in seven piglets during 7 h of monotonous mechanical ventilation. During the 1st h of ventilation, every heartbeat triggered a noticeable transient increase in lung volume of 14 ml (95% confidence interval = 10-17 ml). After 7 h, the increase in lung volume due to heartbeat significantly decreased to 7 ml (95% confidence interval = 2-9 ml, P < 0.05). During the course of ventilation, overall lung compliance and gas exchange were progressively compromised. We conclude that 1) sufficient mechanical energy is transferred from the beating heart to the lung to increase lung volume, and 2) the ability of the heartbeats to help increase lung volume is reduced during long-term ventilation, which reflects the changes in lung compliance.