Search

Tocilizumab is a monoclonal antibody that interrupts interleukin-6 signalling, reducing downstream effects on inflammation and the innate immune response. It was shown to reduce mortality in patients with severe or critical coronavirus disease 2019 (COVID-19). Pregnant and breastfeeding people were largely excluded from clinical trials and hence, the extent to which results can be applied to these populations is not clear. To synthesize published data on tocilizumab in pregnancy and lactation, highlight important knowledge gaps, and help inform clinical decision-making about tocilizumab's use in these populations with COVID-19. PubMed was searched for studies evaluating tocilizumab in pregnancy and lactation for COVID-19 and other indications. Literature on pharmacokinetics and reproductive/fetal safety of monoclonal antibodies in general was also sought. The US Food and Drug Administration and the European Medicines Agency guidance for the industry and regulatory approval documents were reviewed. Published data on tocilizumab in pregnancy include 610 cases (n = 20 with COVID-19) together with seven mother–infant breastfeeding pairs. Higher rates of spontaneous abortion and premature birth have been reported compared with the general population, but multiple confounding variables limit interpretation. There is little data on tocilizumab exposure in the second and third trimesters when transplacental transport is highest. The effects of tocilizumab on the developing immune system are unclear. Pregnant patients with COVID-19 who received tocilizumab were often critically ill and corticosteroid use was uncommon. Neonatal follow up was limited. Tocilizumab appears to be compatible with breastfeeding. Although the available data do not raise serious safety signals, they have significant limitations and are not sufficient to delineate the complete spectrum of potential adverse outcomes that may be associated with tocilizumab exposure during pregnancy and lactation. Diligent follow up and documentation of pregnancy outcomes will be important moving forward. A more effective regulatory framework to ensure equitable inclusion of pregnant people in research is clearly needed. [ABSTRACT FROM AUTHOR]

Purpose: Pregnancy-related critical illness leads to death for 3–14% of affected women. Although identifying patients at risk could facilitate preventive strategies, guide therapy, and help in clinical research, no prior systematic review of this literature exploring the validity of risk prediction models for maternal mortality exists. Therefore, we have systematically reviewed and meta-analyzed risk prediction models for maternal mortality. Methods: Search strategy: MEDLINE, EMBASE and Scopus, from inception to May 2017. Selection criteria: Trials or observational studies evaluating risk prediction models for maternal mortality. Data collection and analysis: Two reviewers independently assessed studies for eligibility and methodological quality, and extracted data on prediction performance. Results: Thirty-eight studies that evaluated 12 different mortality prediction models were included. Mortality varied across the studies, with an average rate 10.4%, ranging from 0 to 41.7%. The Collaborative Integrated Pregnancy High-dependency Estimate of Risk (CIPHER) model and the Maternal Severity Index had the best performance, were developed and validated from studies of obstetric population with a low risk of bias. The CIPHER applies to critically ill obstetric patients (discrimination: area under the receiver operating characteristic curve (AUC) 0.823 (0.811–0.835), calibration: graphic plot [intercept—0.09, slope 0.92]). The Maternal Severity Index applies to hospitalized obstetric patients (discrimination: AUC 0.826 [0.802–0.851], calibration: standardized mortality ratio 1.02 [0.86–1.20]). Conclusions: Despite the high heterogeneity of the study populations and the limited number of studies validating the finally eligible prediction models, the CIPHER and the Maternal Severity Index are recommended for use among critically ill and hospitalized pregnant and postpartum women for risk adjustment in clinical research and quality improvement studies. Neither index has sufficient discrimination to be applicable for clinical decision making at the individual patient level. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Respiratory failure affects up to 0.2% of pregnancies, more commonly in the postpartum period. Altered maternal respiratory physiology affects the assessment and management of these patients. Respiratory failure may result from pregnancy-specific conditions such as preeclampsia, amniotic fluid embolism or peripartum cardiomyopathy. Pregnancy may increase the risk or severity of other conditions, including thromboembolism, asthma, viral pneumonitis, and gastric acid aspiration. Management during pregnancy is similar to the nonpregnant patient. Endotracheal intubation in pregnancy carries an increased risk, due to airway edema and rapid oxygen desaturation following apnea. Few data are available to direct prolonged mechanical ventilation in pregnancy. Chest wall compliance is reduced, perhaps permitting slightly higher airway pressures. Optimizing oxygenation is important, but data on the use of permissive hypercapnia are limited. Delivery of the fetus does not always improve maternal respiratory function, but should be considered if benefit to the fetus is anticipated. [ABSTRACT FROM AUTHOR]

Keywords: critical care; high-risk pregnancy; intensive care; maternal morbidity; maternal mvortality; risk prediction; severity of illness EN critical care high-risk pregnancy intensive care maternal morbidity maternal mvortality risk prediction severity of illness 765 766 2 04/21/20 20200501 NES 200501 Maternal mortality represents a catastrophic end to pregnancy, with marked heterogeneity in frequency occurring across the world. In this issue of I Critical Care Medicine i , the Intensive Care National Audit and Research Centre (ICNARC) have used their large Case Mix Program database (CMPDB) from United Kingdom, Wales, and Northern Ireland to develop a risk prediction model for the pregnant patient by Simpson et al ([5]). Mortality of pregnant ICU patients in the CMPDB was 1.7%, lower than the systematic review which reported a mortality in pregnant ICU patients of 3.4% in developed countries and 14% in developing countries ([2]). [Extracted from the article]

The author reflects on the study which investigates the risk of lung injury during pregnancy in a rabbit model. He describes the two-hit mechanism as demonstrated in the study which involves the induction of hemorrhagic shock followed by resuscitation. He stresses that acute respiratory distress syndrome (ARDS) occurred 10 times more frequently in pregnat women compared to the general population.

The article focuses on pregnancy-related admissions to the intensive care unit (ICU) with emphasis on the quality of care given to fetuses of critically ill mothers. It cites an overview of the study conducted by several researchers and their utilization of analysis tools and associated materials in identifying risk factors, behavior mechanisms and other conditions related to efficient health care delivery. It also discusses the investigations conducted to construe interventions in these cases.

Abstract: Purpose: To test discrimination and calibration of APACHE-II and SAPS-II risk prediction scores in a cohort of obstetric patients, and to evaluate the effect of modifying these scores for the physiological changes in pregnancy. Materials and Methods: A retrospective review of obstetric patients, 12 weeks gestation to 48 hours postpartum, admitted to the ICU for more than 24 hours. APACHE-II and SAPS-II, and versions modified for the physiological changes of pregnancy, were evaluated by receiver operating characteristic (ROC) curves and standardized mortality ratios (SMR). Multivariable analysis identified other parameters associated with mortality. Results: Data were obtained from 332 patients from 5 countries, with a mortality rate of 12%. Mean (± SD) APACHE-II score was 16.8 ± 6.1 and SAPS-II score 26.5 ± 15.8. Good discrimination was demonstrated with area under the ROC curves of 0.82 and 0.78 respectively, with no improvement after modification for altered maternal physiology. APACHE-II overestimated mortality, with an SMR of 0.43 (0.52 after including diagnostic weighting) compared with 0.89 for SAPS-II. Bilirubin, albumin and Glasgow Coma Scale were independently associated with mortality. Conclusion: APACHE-II and SAPS-II are good discriminators of illness severity and may be valuable for comparing obstetric cohorts, but APACHE-II significantly over-estimates mortality. [Copyright &y& Elsevier]

Severe complications of infectious diseases can occur during pregnancy. Evidence-based prevention and treatment strategies are critical to improve maternal and neonatal health outcomes. Despite this medical need, pregnant and breastfeeding people have been systematically excluded from biomedical research. The objective of this study was to characterize representation of pregnant and breastfeeding people in randomized controlled trials (RCTs) evaluating a broad range of interventions for infectious diseases. Pregnancy and breastfeeding inclusion criteria were examined in infectious diseases RCTs published between 1 January 2017, and 31 December 2019, in the top five highest impact general medicine and the top three highest impact infectious diseases and HIV journals. Of 376 RCTs, 5.3% and 1.9% included pregnant and breastfeeding people, respectively. Justification for exclusion was documented in 36/271 (13.3%) studies that explicitly excluded pregnant people. Most studies excluding pregnant people (177/271, 65.3%) required at least one form of contraception, abstinence and/or negative pregnancy test(s) as part of participation. Only 11/271 (4.1%) studies excluding pregnant people allowed participants to continue the intervention if unintended pregnancy occurred during the study. When both pregnant and non-pregnant people were eligible, pregnant people made up <3% of participants. Only 2/48 (4.2%) vaccine studies included pregnant people; 13/234 (5.5%) drug studies included pregnant people. All studies of procedures, devices, behaviour/education and supplements/vitamins explicitly excluded or did not address pregnancy eligibility criteria. Only 2/20 (10.0%) RCTs including pregnant people collected pharmacokinetic data. This study demonstrates widespread exclusion of pregnant and breastfeeding people from infectious disease RCTs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]