Critical Care Services for Pregnant Patients in Ontario: A Province-Wide Survey.

Critically ill pregnant patients require advanced critical care support, but access to these services is variable. We surveyed active Ontario obstetric facilities regarding critical care access. Responses were received from 44 of 80 obstetric units (55%), 13 (30%) being rural. Transport to another facility was required by 59% (majority >1 hour transport time), and differences were noted in the availability of specialty support services such as anesthesia and internal/obstetric medicine, as well as radiology and laboratory facilities, and use of massive transfusion protocols. Training in early supportive care of obstetric complications and optimized facility transport are areas for potential improvement.

A review of remdesivir for COVID-19 in pregnancy and lactation.

Mounting evidence suggests that pregnant people have an elevated risk of severe COVID-19-related complications compared with their non-pregnant counterparts, underscoring the need for effective prevention and treatment strategies. However, despite progress in innovative and flexible trial designs during the COVID-19 pandemic, regressive policies excluding pregnant and breastfeeding people from biomedical research persist. Remdesivir, a broad-spectrum antiviral, was the first drug licensed for the treatment of COVID-19, based on data showing it reduced the time to recovery in hospitalized patients. Pregnant and breastfeeding people were specifically excluded from all clinical trials of remdesivir in COVID-19, but data are accumulating from post-marketing registries, compassionate use programmes and case series/reports. In this review we synthesize these data and highlight key knowledge gaps to help inform clinical decision-making about its use in pregnancy and lactation.

Long-Term Effects of Phased Implementation of Antimicrobial Stewardship in Academic ICUs: 2007-2015.

OBJECTIVES: Antimicrobial stewardship is advocated to reduce antimicrobial resistance in ICUs by reducing unnecessary antimicrobial consumption. Evidence has been limited to short, single-center studies. We evaluated whether antimicrobial stewardship in ICUs could reduce antimicrobial consumption and costs. DESIGN: We conducted a phased, multisite cohort study of a quality improvement initiative. SETTING: Antimicrobial stewardship was implemented in four academic ICUs in Toronto, Canada beginning in February 2009 and ending in July 2012. PATIENTS: All patients admitted to each ICU from January 1, 2007, to December 31, 2015, were included. INTERVENTIONS: Antimicrobial stewardship was delivered using in-person coaching by pharmacists and physicians three to five times weekly, and supplemented with unit-based performance reports. Total monthly antimicrobial consumption (measured by defined daily doses/100 patient-days) and costs (Canadian dollars/100 patient-days) before and after antimicrobial stewardship implementation were measured. MEASUREMENTS AND MAIN RESULTS: A total of 239,123 patient-days (57,195 patients) were analyzed, with 148,832 patient-days following introduction of antimicrobial stewardship. Antibacterial use decreased from 120.90 to 110.50 defined daily dose/100 patient-days following introduction of antimicrobial stewardship (adjusted intervention effect -12.12 defined daily dose/100 patient-days; 95% CI, -16.75 to -7.49; p < 0.001) and total antifungal use decreased from 30.53 to 27.37 defined daily doses/100 patient-days (adjusted intervention effect -3.16 defined daily dose/100 patient-days; 95% CI, -8.33 to 0.04; p = 0.05). Monthly antimicrobial costs decreased from $3195.56 to $1998.59 (adjusted intervention effect -$642.35; 95% CI, -$905.85 to -$378.84; p < 0.001) and total antifungal costs were unchanged from $1771.86 to $2027.54 (adjusted intervention effect -$355.27; 95% CI, -$837.88 to $127.33; p = 0.15). Mortality remained unchanged, with no consistent effects on antimicrobial resistance and candidemia. CONCLUSIONS: Antimicrobial stewardship in ICUs with coaching plus audit and feedback is associated with sustained improvements in antimicrobial consumption and cost. ICUs with high antimicrobial consumption or expenditure should consider implementing antimicrobial stewardship programs.

Variability in intensive care unit admission among pregnant and postpartum women in Canada: a nationwide population-based observational study.

BACKGROUND: Pregnancy-related critical illness results in approximately 300,000 deaths globally each year. The objective was to describe the variation in ICU admission and the contribution of patient- and hospital-based factors in ICU admission among acute care hospitals for pregnant and postpartum women in Canada. METHODS: A nationwide cohort study between 2004 and 2015, comprising all pregnant or postpartum women admitted to Canadian hospitals. The primary outcome was ICU admission. Secondary outcomes were severe maternal morbidity (a potentially life-threatening condition) and maternal death (during and within 6 weeks after pregnancy). The proportion of total variability in ICU admission rates due to the differences among hospitals was described using the median odds ratio from multi-level logistic regression models, adjusting for individual hospital clusters. RESULTS: There were 3,157,248 identifiable pregnancies among women admitted to 342 Canadian hospitals. The overall ICU admission rate was 3.2 per 1000 pregnancies. The rate of severe maternal morbidity was 15.8 per 1000 pregnancies, of which 10% of women were admitted to an ICU. The most common severe maternal morbidity events included postpartum hemorrhage (n = 16,364, 0.52%) and sepsis (n = 11,557, 0.37%). Of the 195 maternal deaths (6.2 per 100,000 pregnancies), only 130 (67%) were admitted to ICUs. Patients dying in hospital, without admission to ICU, included those with cardiovascular compromise, hemorrhage, and sepsis. For 2 pregnant women with similar characteristics at different hospitals, the average (median) odds of being admitted to ICU was 1.92 in 1 hospital compared to another. Hospitals admitting the fewest number of pregnant patients had the highest incidence of severe maternal morbidity and mortality. Patient-level factors associated with ICU admission were maternal comorbidity index (OR 1.88 per 1 unit increase, 95%CI 1.86-1.99), urban residence (OR 1.09, 95%CI 1.02-1.16), and residing at the lowest income quintile (OR 1.44, 95%CI 1.34-1.55). CONCLUSIONS: Most women who experience severe maternal morbidity are not admitted to an ICU. There exists a wide hospital-level variability in ICU admission, with patients living in urban locations and patients of lowest income levels most likely to be admitted to ICU. Cardiovascular compromise, hemorrhage, and sepsis represent an opportunity for improved patient care and outcomes.

Temporal Variations in Incidence andOutcomes of Critical Illness Among Pregnant and Postpartum Women inCanada: A Population-Based Observational Study.

OBJECTIVE: Pregnancy-associated morbidity results in hundreds of thousands of deaths annually worldwide. Reducing maternal mortality is a key United Nations Millennium Development Goal. Although maternal mortality has declined in high-income countries, contemporary estimates of maternal morbidity and mortality trends in Canada are lacking. METHODS: This population-based study investigated all antepartum, peripartum, and postpartum women presenting to an acute care hospital in Canada from April 1, 2004 to March 31, 2015. The primary outcome was the change in rates of severe maternal morbidity over time. Secondary outcomes included severe maternal mortality and intensive care unit admission, including by province and territory (level of evidence: II2). RESULTS: The cohort comprised 2 035 453 mothers with 3 162 303 pregnancies. There were 17.7 per 1000 episodes of severe maternal morbidity, with annual increases of 1.3% (95% confidence interval [CI] 0.60-2.0) for severe maternal morbidity. The maternal mortality rate was 6.2 per 100 000 deliveries and stable over time (estimated percentage of annual change of -0.46%; 95% CI -5.0 to 4.3). The most common causes of severe maternal morbidity were postpartum hemorrhage (5.5 per 1000 deliveries), sepsis (3.8 per 1,000 deliveries), and cardiac failure (1.5 per 1000 deliveries). Severe maternal morbidity varied across Canadian regions but was highest in the Territories at 22.8 per 1000 deliveries. CONCLUSION: Although maternal mortality has been stable in Canada over time, rates of severe maternal morbidity are increasing and are associated with substantial regional variation, with the highest rates experienced by women in the northern Territories.

Deresuscitation of Patients With Iatrogenic Fluid Overload Is Associated With Reduced Mortality in Critical Illness.

OBJECTIVES: To characterize current practice in fluid administration and deresuscitation (removal of fluid using diuretics or renal replacement therapy), the relationship between fluid balance, deresuscitative measures, and outcomes and to identify risk factors for positive fluid balance in critical illness. DESIGN: Retrospective cohort study. SETTING: Ten ICUs in the United Kingdom and Canada. PATIENTS: Adults receiving invasive mechanical ventilation for a minimum of 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred patients were included. Positive cumulative fluid balance (fluid input greater than output) occurred in 87.3%: the largest contributions to fluid input were from medications and maintenance fluids rather than resuscitative IV fluids. In a multivariate logistic regression model, fluid balance on day 3 was an independent risk factor for 30-day mortality (odds ratio 1.26/L [95% CI, 1.07-1.46]), whereas negative fluid balance achieved in the context of deresuscitative measures was associated with lower mortality. Independent predictors of greater fluid balance included treatment in a Canadian site. CONCLUSIONS: Fluid balance is a practice-dependent and potentially modifiable risk factor for adverse outcomes in critical illness. Negative fluid balance achieved with deresuscitation on day 3 of ICU stay is associated with improved patient outcomes. Minimization of day 3 fluid balance by limiting maintenance fluid intake and drug diluents, and using deresuscitative measures, represents a potentially beneficial therapeutic strategy which merits investigation in randomized trials.

Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model.

BACKGROUND: Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care. METHODS: A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration. RESULTS: Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08). CONCLUSIONS: The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.

Sepsis now a priority: a quality improvement initiative for early sepsis recognition and care.

OBJECTIVE: To develop a triage-based screening algorithm and treatment order-sets aimed at improving the quality of care of all patients with sepsis presenting to our emergency department (ED). DESIGN: Retrospective cohort study conducted during a pre-intervention period from 1 April 2010 to 31 March 2011 and a post-intervention period from 1 September 2014 to 30 April 2015. SETTING: A large teaching hospital located in Toronto, Ontario, Canada with a 35-bed ED. PARTICIPANTS: All patients meeting pre-specified sepsis criteria during the ED encounter. MAIN OUTCOME MEASURES: Process of care measures included time to assessment by emergency physician, lactate measurement, blood culture collection, fluid and antibiotic administration. Intensive care unit (ICU) outcomes including admissions, length of stay (LOS) and deaths were reviewed. RESULTS: There were 346 patients pre-intervention, and 270 patients post-intervention. We significantly improved all process measures including mean time to antibiotics by 60 min (P = 0.003) and proportion of patients receiving fluid resuscitation (64.7% vs. 94.4%, P < 0.001). There was no significant difference in the number of patients admitted to ICU (P = 0.14). The median ICU LOS was shorter in the post-intervention group [2.0 days (interquartile range (IQR) 1.0-4.5 days) vs. 5.0 days (IQR 1.5-10.8 days), P = 0.04], and there was no difference in in-hospital mortality between groups (P = 0.27). CONCLUSIONS: We have demonstrated that a triage-based sepsis screening tool results in expedited and consistent delivery of care, with a significant improvement in initial resuscitation measures.

Management of Acute Respiratory Failure in Pregnancy.

Respiratory failure affects up to 1 in 500 pregnancies, more commonly in the postpartum period. The causes of respiratory failure include several pregnancy-specific conditions such as preeclampsia, amniotic fluid embolism, and peripartum cardiomyopathy. Pregnancy may also increase the risk or severity of other conditions, such as asthma, thromboembolism, viral pneumonitis, and gastric acid aspiration. Changes to maternal respiratory physiology and the presence of a fetus may affect the assessment and management of these patients. In addition to identifying pregnancy-specific causes, some differences exist in the management of the pregnant woman with acute respiratory failure. Endotracheal intubation in pregnancy carries a significant risk, due to upper airway edema and rapid oxygen desaturation following apnea. Few studies have addressed prolonged mechanical ventilation management in pregnancy. Optimizing oxygenation is important, but whether permissive hypercapnia is tolerated during pregnancy remains unclear. Delivery of the fetus is often considered but does not always improve maternal respiratory function and should be reserved only for cases where benefit to the fetus is anticipated.

Measurement properties of comorbidity indices in maternal health research: a systematic review.

BACKGROUND: Maternal critical illness occurs in 1.2 to 4.7 of every 1000 live births in the United States and approximately 1 in 100 women who become critically ill will die. Patient characteristics and comorbid conditions are commonly summarized as an index or score for the purpose of predicting the likelihood of dying; however, most such indices have arisen from non-pregnant patient populations. We sought to systematically review comorbidity indices used in health administrative datasets of pregnant women, in order to critically appraise their measurement properties and recommend optimal tools for clinicians and maternal health researchers. METHODS: We conducted a systematic search of MEDLINE and EMBASE to identify studies published from 1946 and 1947, respectively, to May 2017 that describe predictive validity of comorbidity indices using health administrative datasets in the field of maternal health research. We applied a methodological PubMed search filter to identify all studies of measurement properties for each index. RESULTS: Our initial search retrieved 8944 citations. The full text of 61 articles were identified and assessed for final eligibility. Finally, two eligible articles, describing three comorbidity indices appropriate for health administrative data remained: The Maternal comorbidity index, the Charlson comorbidity index and the Elixhauser Comorbidity Index. These studies of identified indices had a low risk of bias. The lack of an established consensus-building methodology in generating each index resulted in marginal sensibility for all indices. Only the Maternal Comorbidity Index was derived and validated specifically from a cohort of pregnant and postpartum women, using an administrative dataset, and had an associated c-statistic of 0.675 (95% Confidence Interval 0.647-0.666) in predicting mortality. CONCLUSIONS: Only the Maternal Comorbidity Index directly evaluated measurement properties relevant to pregnant women in health administrative datasets; however, it has only modest predictive ability for mortality among development and validation studies. Further research to investigate the feasibility of applying this index in clinical research, and its reliability across a variety of health administrative datasets would be incrementally helpful. Evolution of this and other tools for risk prediction and risk adjustment in pregnant and post-partum patients is an important area for ongoing study.

Cardiac Arrest in Pregnancy: A Scientific Statement From the American Heart Association.

This is the first scientific statement from the American Heart Association on maternal resuscitation. This document will provide readers with up-to-date and comprehensive information, guidelines, and recommendations for all aspects of maternal resuscitation. Maternal resuscitation is an acute event that involves many subspecialties and allied health providers; this document will be relevant to all healthcare providers who are involved in resuscitation and specifically maternal resuscitation.

Severe Staphylococcus aureus Endocarditis Presenting as Peripartum Thrombotic Thrombocytopenic Purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening illness that occurs in both pregnant and non-pregnant women. Several other conditions can mimic the disease, which makes the diagnosis challenging. CASE: We describe a case of severe Staphylococcus aureus endocarditis that initially presented as peripartum TTP in a 39-year-old woman at 29+6 weeks' gestation. We give an overview of the diagnostic considerations and management of thrombocytopenia in pregnancy and review the literature related to TTP and peripartum infective endocarditis. CONCLUSION: Given the significant differences in definitive therapies for the spectrum of thrombocytopenic conditions that occur in pregnancy, timely and accurate diagnosis of TTP is critical for optimal management.

Endotracheal intubation in the ICU.

Endotracheal intubation in the ICU is a high-risk procedure, resulting in significant morbidity and mortality. Up to 40% of cases are associated with marked hypoxemia or hypotension. The ICU patient is physiologically very different from the usual patient who undergoes intubation in the operating room, and different intubation techniques should be considered. The common operating room practice of sedation and neuromuscular blockade to facilitate intubation may carry significant risk in the ICU patient with a marked oxygenation abnormality, particularly when performed by the non-expert. Preoxygenation is largely ineffective in these patients and oxygen desaturation occurs rapidly on induction of anesthesia, limiting the time available to secure the airway. The ICU environment is less favorable for complex airway management than the operating room, given the frequent lack of availability of additional equipment or additional expert staff. ICU intubations are frequently carried out by trainees, with a lesser degree of airway experience. Even in the presence of a non-concerning airway assessment, these patients are optimally managed as a difficult airway, utilizing an awake approach. Endotracheal intubation may be achieved by awake direct laryngoscopy in the sick ICU patient whose level of consciousness may be reduced by sepsis, hypercapnia or hypoxemia. As the patient's spontaneous respiratory efforts are not depressed by the administration of drugs, additional time is available to obtain equipment and expertise in the event of failure to secure the airway. ICU intubation complications should be tracked as part of the ICU quality improvement process.

Interaction between fluids and vasoactive agents on mortality in septic shock: a multicenter, observational study.

OBJECTIVE: Fluids and vasoactive agents are both used to treat septic shock, but little is known about how they interact or the optimal way to administer them. We sought to determine how hospital mortality was influenced by combined use of these two treatments. DESIGN: Retrospective evaluation using multivariable logistic regression to evaluate the association between hospital mortality and categorical variables representing initiation of vasoactive agents and volumes of IV fluids given 0-1, 1-6, and 6-24 hours after onset, including interactions and adjusting for potential confounders. SETTING: ICUs of 24 hospitals in 3 countries. PATIENTS: Two thousand eight hundred forty-nine patients who survived more than 24 hours after after onset of septic shock, admitted between 1989 and 2007. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fluids and vasoactive agents had strong, interacting associations with mortality (p < 0.0001). Mortality was lowest when vasoactive agents were begun 1-6 hours after onset, with more than 1 L of fluids in the initial hour after shock onset, more than 2.4 L from hours 1-6, and 1.6-3.5 L from 6 to 24 hours. The lowest mortality rates were associated with starting vasoactive agents 1-6 hours after onset. CONCLUSIONS: The focus during the first hour of resuscitation for septic shock should be aggressive fluid administration, only thereafter starting vasoactive agents, while continuing aggressive fluid administration. Starting vasoactive agents in the initial hour may be detrimental, and not all of that association is due to less fluids being given with such early initiation of vasoactive agents.

Fetal outcome in the critically ill pregnant woman.

Management of the critically ill pregnant woman is complicated by potential adverse effects of both maternal illness and ICU interventions on the fetus. This paper reviews the potential risks to the fetus of maternal critical illness, including shock, hypoxemia, and fever, as well as the effects of critical care management, such as drug therapy and radiological investigations. The authors' recommended approach to management is provided. Prior publications and new data presented identify that there is insufficient information to prognosticate accurately on fetal outcome after maternal critical illness, although maternal shock, hypoxemia and early gestational age are likely significant risk factors.

Fluid balance, intradialytic hypotension, and outcomes in critically ill patients undergoing renal replacement therapy: a cohort study.

INTRODUCTION: In this cohort study, we explored the relationship between fluid balance, intradialytic hypotension and outcomes in critically ill patients with acute kidney injury (AKI) who received renal replacement therapy (RRT). METHODS: We analysed prospectively collected registry data on patients older than 16 years who received RRT for at least two days in an intensive care unit at two university-affiliated hospitals. We used multivariable logistic regression to determine the relationship between mean daily fluid balance and intradialytic hypotension, both over seven days following RRT initiation, and the outcomes of hospital mortality and RRT dependence in survivors. RESULTS: In total, 492 patients were included (299 male (60.8%), mean (standard deviation (SD)) age 62.9 (16.3) years); 251 (51.0%) died in hospital. Independent risk factors for mortality were mean daily fluid balance (odds ratio (OR) 1.36 per 1000 mL positive (95% confidence interval (CI) 1.18 to 1.57), intradialytic hypotension (OR 1.14 per 10% increase in days with intradialytic hypotension (95% CI 1.06 to 1.23)), age (OR 1.15 per five-year increase (95% CI 1.07 to 1.25)), maximum sequential organ failure assessment score on days 1 to 7 (OR 1.21 (95% CI 1.13 to 1.29)), and Charlson comorbidity index (OR 1.28 (95% CI 1.14 to 1.44)); higher baseline creatinine (OR 0.98 per 10 µmol/L (95% CI 0.97 to 0.996)) was associated with lower risk of death. Of 241 hospital survivors, 61 (25.3%) were RRT dependent at discharge. The only independent risk factor for RRT dependence was pre-existing heart failure (OR 3.13 (95% CI 1.46 to 6.74)). Neither mean daily fluid balance nor intradialytic hypotension was associated with RRT dependence in survivors. Associations between these exposures and mortality were similar in sensitivity analyses accounting for immortal time bias and dichotomising mean daily fluid balance as positive or negative. In the subgroup of patients with data on pre-RRT fluid balance, fluid overload at RRT initiation did not modify the association of mean daily fluid balance with mortality. CONCLUSIONS: In this cohort of patients with AKI requiring RRT, a more positive mean daily fluid balance and intradialytic hypotension were associated with hospital mortality but not with RRT dependence at hospital discharge in survivors.