Intensive care implications of epidemic thunderstorm asthma.

OBJECTIVE: To investigate the environmental precipitants, treatment and outcome of critically ill patients affected by the largest and most lethal reported epidemic of thunderstorm asthma. DESIGN, SETTING AND PARTICIPANTS: Retrospective multicentre observational study. Meteorological, airborne particulate and pollen data, and a case series of 35 patients admitted to 15 intensive care units (ICUs) due to the thunderstorm asthma event of 21-22 November 2016, in Victoria, Australia, were analysed and compared with 1062 total ICU-admitted Australian patients with asthma in 2016. MAIN OUTCOME MEASURES: Characteristics and outcomes of total ICU versus patients with thunderstorm asthma, the association between airborne particulate counts and storm arrival, and ICU resource utilisation. RESULTS: All 35 patients had an asthma diagnosis; 13 (37%) had a cardiac or respiratory arrest, five (14%) died. Compared with total Australian ICU-admitted patients with asthma in 2016, patients with thunderstorm asthma had a higher mortality (15% v 1.3%, P < 0.001), were more likely to be male (63% v 34%, P < 0.001), to be mechanically ventilated, and had shorter ICU length of stay in survivors (median, 31.8 hours [interquartile range (IQR), 14.8-43.6 hours] v 40.7 hours [IQR, 22.3-75.1 hours]; P = 0.025). Patients with cardiac arrest were more likely to be born in Asian or subcontinental countries (5/10 [50%] v 4/25 [16%]; relative risk, 3.13; 95% CI, 1.05-9.31). A temporal link was demonstrated between airborne particulate counts and arrival of the storm. The event used 15% of the public ICU beds in the region. CONCLUSION: Arrival of a triggering storm is associated with an increase in respirable airborne particles. Affected critically ill patients are young, have a high mortality, a short duration of bronchospasm, and a prior diagnosis of asthma is common.

Ventilation management in Victorian intensive care unit patients without acute respiratory distress syndrome.

BACKGROUND: The setting of tidal volume (VT) during controlled mechanical ventilation (CMV) in critically ill patients without acute respiratory distress syndrome (ARDS) is likely important but currently unknown. We aimed to describe current CMV settings in intensive care units (ICUs) across Victoria. METHODS: We performed a multicentre, prospective, observational study. We collected clinical, ventilatory and arterial blood gas data twice daily for 7 days. We performed subgroup analysis by sex and assessment of arterial partial pressure of carbon dioxide (PaCO2) management where hypercapnia was potentially physiologically contraindicated. RESULTS: We recorded 453 observational sets in 123 patients across seven ICUs. The most commonly selected initial VT was 500 mL (33%), and this proportion did not differ according to sex (32% male, 34% female). Moreover, 38% of patients were exposed to initial VT per predicted body weight (VT-PBW) > 8.0 mL/kg. VT-PBW in this range were more likely to occur in females, those with a lower height, lower ideal body weight or in those for whom hypercapnia was potentially physiologically contraindicated. As a consequence, females were more frequently exposed to a lower PaCO2 and higher pH. CONCLUSIONS: In adults without ARDS undergoing CMV in Australian ICUs, the initial VT was a stereotypical 500 mL in one-third of participants, irrespective of sex. Moreover, around 40% of patients were exposed to an initial VT-PBW > 8.0 mL/kg. Finally, women were more likely to be exposed to a high VT and hyperventilation.

The Melbourne epidemic thunderstorm asthma event 2016: an investigation of environmental triggers, effect on health services, and patient risk factors.

BACKGROUND: A multidisciplinary collaboration investigated the world's largest, most catastrophic epidemic thunderstorm asthma event that took place in Melbourne, Australia, on Nov 21, 2016, to inform mechanisms and preventive strategies. METHODS: Meteorological and airborne pollen data, satellite-derived vegetation index, ambulance callouts, emergency department presentations, and data on hospital admissions for Nov 21, 2016, as well as leading up to and following the event were collected between Nov 21, 2016, and March 31, 2017, and analysed. We contacted patients who presented during the epidemic thunderstorm asthma event at eight metropolitan health services (each including up to three hospitals) via telephone questionnaire to determine patient characteristics, and investigated outcomes of intensive care unit (ICU) admissions. FINDINGS: Grass pollen concentrations on Nov 21, 2016, were extremely high (>100 grains/m3). At 1800 AEDT, a gust front crossed Melbourne, plunging temperatures 10°C, raising humidity above 70%, and concentrating particulate matter. Within 30 h, there were 3365 (672%) excess respiratory-related presentations to emergency departments, and 476 (992%) excess asthma-related admissions to hospital, especially individuals of Indian or Sri Lankan birth (10% vs 1%, p<0·0001) and south-east Asian birth (8% vs 1%, p<0·0001) compared with previous 3 years. Questionnaire data from 1435 (64%) of 2248 emergency department presentations showed a mean age of 32·0 years (SD 18·6), 56% of whom were male. Only 28% had current doctor-diagnosed asthma. 39% of the presentations were of Asian or Indian ethnicity (25% of the Melbourne population were of this ethnicity according to the 2016 census, relative risk [RR] 1·93, 95% CI 1·74-2·15, p <0·0001). Of ten individuals who died, six were Asian or Indian (RR 4·54, 95% CI 1·28-16·09; p=0·01). 35 individuals were admitted to an intensive care unit, all had asthma, 12 took inhaled preventers, and five died. INTERPRETATION: Convergent environmental factors triggered a thunderstorm asthma epidemic of unprecedented magnitude, tempo, and geographical range and severity on Nov 21, 2016, creating a new benchmark for emergency and health service escalation. Asian or Indian ethnicity and current doctor-diagnosed asthma portended life-threatening exacerbations such as those requiring admission to an ICU. Overall, the findings provide important public health lessons applicable to future event forecasting, health care response coordination, protection of at-risk populations, and medical management of epidemic thunderstorm asthma. FUNDING: None.

Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial).

BACKGROUND: In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. METHODS: In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. RESULTS: We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31). CONCLUSIONS: In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment.

Arterial oxygen tension and mortality in mechanically ventilated patients.

PURPOSE: Early hyperoxia may be an independent risk factor for mortality in mechanically ventilated intensive care unit (ICU) patients. We examined the relationship between early arterial oxygen tension (PaO(2)) and in-hospital mortality. METHOD: We retrospectively assessed arterial blood gases (ABG) with 'worst' alveolar-arterial (A-a) gradient during the first 24 h of ICU admission for all ventilated adult patients from 150 participating ICUs between 2000 and 2009. We used multivariate analysis in all patients and defined subgroups to determine the relationship between PaO(2) and mortality. We also studied the relationship between worst PaO(2), admission PaO(2) and peak PaO(2) in a random cohort of patients. RESULTS: We studied 152,680 patients. Their mean PaO(2) was 20.3 kPa (SD 14.6) and mean inspired fraction of oxygen (FiO(2)) was 62% (SD 26). Worst A-a gradient ABG identified that 49.8% (76,110) had hyperoxia (PaO(2) > 16 kPa). Nineteen per cent of patients died in ICU and 26% in hospital. After adjusting for site, Simplified Acute Physiology Score II (SAPS II), age, FiO(2), surgical type, Glasgow Coma Scale (GCS) below 15 and year of ICU admission, there was an association between progressively lower PaO(2) and increasing in-hospital mortality, but not with increasing levels of hyperoxia. Similar findings were observed with a sensitivity analysis of PaO(2) derived from high FiO(2) (≥50%) versus low FiO(2) (<50%) and in defined subgroups. Worst PaO(2) showed a strong correlation with admission PaO(2) (r = 0.98) and peak PaO(2) within 24 h of admission (r = 0.86). CONCLUSION: We found there was an association between hypoxia and increased in-hospital mortality, but not with hyperoxia in the first 24 h in ICU and mortality in ventilated patients. Our findings differ from previous studies and suggest that the impact of early hyperoxia on mortality remains uncertain.

Acquired bloodstream infection in the intensive care unit: incidence and attributable mortality.

INTRODUCTION: To estimate the incidence of intensive care unit (ICU)-acquired bloodstream infection (BSI) and its independent effect on hospital mortality. METHODS: We retrospectively studied acquisition of BSI during admissions of >72 hours to adult ICUs from two university-affiliated hospitals. We obtained demographics, illness severity and co-morbidity data from ICU databases and microbiological diagnoses from departmental electronic records. We assessed survival at hospital discharge or at 90 days if still hospitalized. RESULTS: We identified 6339 ICU admissions, 330 of which were complicated by BSI (5.2%). Median time to first positive culture was 7 days (IQR 5-12). Overall mortality was 23.5%, 41.2% in patients with BSI and 22.5% in those without. Patients who developed BSI had higher illness severity at ICU admission (median APACHE III score: 79 vs. 68, P < 0.001). After controlling for illness severity and baseline demographics by Cox proportional-hazard model, BSI remained independently associated with risk of death (hazard ratio from diagnosis 2.89; 95% confidence interval 2.41-3.46; P < 0.001). However, only 5% of the deaths in this model could be attributed to acquired-BSI, equivalent to an absolute decrease in survival of 1% of the total population. When analyzed by microbiological classification, Candida, Staphylococcus aureus and gram-negative bacilli infections were independently associated with increased risk of death. In a sub-group analysis intravascular catheter associated BSI remained associated with significant risk of death (hazard ratio 2.64; 95% confidence interval 1.44-4.83; P = 0.002). CONCLUSIONS: ICU-acquired BSI is associated with greater in-hospital mortality, but complicates only 5% of ICU admissions and its absolute effect on population mortality is limited. These findings have implications for the design and interpretation of clinical trials.

The interaction of chronic and acute glycemia with mortality in critically ill patients with diabetes.

OBJECTIVES: The relationship between hyperglycemia and mortality is altered by the presence of diabetes mellitus. Biological adjustment to preexisting hyperglycemia might explain this phenomenon. We tested whether the degree of preexisting hyperglycemia would modulate the association between glycemia and outcome during critical illness in patients with diabetes mellitus. DESIGN: Retrospective observational study. SETTING: Two tertiary intensive care units. PATIENTS: Four hundred fifteen critically ill diabetic patients with HbA1c levels measured within 3 months of intensive care unit admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 9,946 blood glucose measurements in this study cohort (glucose measured 6.7 times per day; every 3.6 hrs on average). The median preadmission HbA1c level was 7.0%. There was no significant difference in HbA1c levels (p = .17) or time-weighted average of blood glucose concentrations (p = .49) between survivors and nonsurvivors. The time-weighted average of blood glucose concentrations during intensive care unit stay for nonsurvivors was lower than that of survivors when the HbA1c was >6.8%. In multivariate analysis, we found that there was a significant interaction between HbA1c and the time-weighted glucose level, indicating that the relationship between HbA1c and mortality changed according to the levels of time-weighted average of blood glucose concentrations (p = .008). As a consequence, in patients with higher (>7%) preadmission levels of HbA1c, the higher the time-weighted acute glucose concentration during intensive care unit stay (>10 mmol/L), the lower the hospital mortality compared with the lower HbA1c cohort (<7%). CONCLUSIONS: In patients with diabetes mellitus admitted to intensive care units, there was a significant interaction between preexisting hyperglycemia and the association between acute glycemia and mortality. These observations generate the hypothesis that glucose levels that are considered safe and desirable in other patients might be undesirable in diabetic patients with chronic hyperglycemia. Further studies are required to confirm or refute our findings.

Hypoglycemia and outcome in critically ill patients.

OBJECTIVE: To determine whether mild or moderate hypoglycemia that occurs in critically ill patients is independently associated with an increased risk of death. PATIENTS AND METHODS: Of patients admitted to 2 hospital intensive care units (ICUs) in Melbourne and Sydney, Australia, from January 1, 2000, to October 14, 2004, we analyzed all those who had at least 1 episode of hypoglycemia (glucose concentration, <81 mg/dL). The independent association between hypoglycemia and outcome was statistically assessed. RESULTS: Of 4946 patients admitted to the ICUs, a cohort of 1109 had at least 1 episode of hypoglycemia (blood glucose level, <81 mg/dL). Of these 1109 patients (22.4% of all admissions to the intensive care unit), hospital mortality was 36.6% compared with 19.7% in the 3837 nonhypoglycemic control patients (P<.001). Even patients with a minimum blood glucose concentration between 72 and 81 mg/dL had a greater unadjusted mortality rate than did control patients (25.9% vs 19.7%; unadjusted odds ratio, 1.42; 95% confidence interval, 1.12-1.80; P=.004.) Mortality increased significantly with increasing severity of hypoglycemia (P<.001). After adjustment for insulin therapy, hypoglycemia was independently associated with increased risk of death, cardiovascular death, and death due to infectious disease. CONCLUSION: In critically ill patients, an association exists between even mild or moderate hypoglycemia and mortality. Even after adjustment for insulin therapy or timing of hypoglycemic episode, the more severe the hypoglycemia, the greater the risk of death.

Landmark survival as an end-point for trials in critically ill patients--comparison of alternative durations of follow-up: an exploratory analysis.

INTRODUCTION: Interventional ICU trials have followed up patients for variable duration. However, the optimal duration of follow-up for the determination of mortality endpoint in such trials is uncertain. We aimed to determine the most logical and practical mortality end-point in clinical trials of critically ill patients. METHODS: We performed a retrospective analysis of prospectively collected data involving 369 patients with one of the three specific diagnoses (i) Sepsis (ii) Community acquired pneumonia (iii) Non operative trauma admitted to the Royal Perth Hospital ICU, a large teaching hospital in Western Australia (WA cohort). Their in-hospital and post discharge survival outcome was assessed by linkage to the WA Death Registry. A validation cohort involving 4609 patients admitted during same time period with identical diagnoses from 55 ICUs across Australia (CORE cohort) was used to compare the patient characteristics and in-hospital survival to look at the Australia-wide applicability of the long term survival data from the WA cohort. RESULTS: The long term outcome data of the WA cohort indicate that mortality reached a plateau at 90 days after ICU admission particularly for sepsis and pneumonia. Mortality after hospital discharge before 90 days was not uncommon in these two groups. Severity of acute illness as measured by the total number of organ failures or acute physiology score was the main predictor of 90-day mortality. The adjusted in-hospital survival for the WA cohort was not significantly different from that of the CORE cohort in all three diagnostic groups; sepsis (P = 0.19), community acquired pneumonia (P = 0.86), non-operative trauma (P = 0.47). CONCLUSIONS: A minimum of 90 days follow-up is necessary to fully capture the mortality effect of sepsis and community acquired pneumonia. A shorter period of follow-up time may be sufficient for non-operative trauma.