Pregnancy and COVID-19: pharmacologic considerations.

In this review, we summarize evidence regarding the use of routine and investigational pharmacologic interventions for pregnant and lactating patients with coronavirus disease 2019 (COVID-19). Antenatal corticosteroids may be used routinely for fetal lung maturation between 24 and 34 weeks' gestation, but decisions in those with critical illness and those < 24 or > 34 weeks' gestation should be made on a case-by-case basis. Magnesium sulfate may be used for seizure prophylaxis and fetal neuroprotection, albeit cautiously in those with hypoxia and renal compromise. There are no contraindications to using low-dose aspirin to prevent placenta-mediated pregnancy complications when indicated. An algorithm for thromboprophylaxis in pregnant patients with COVID-19 is presented, which considers disease severity, timing of delivery in relation to disease onset, inpatient vs outpatient status, underlying comorbidities and contraindications to the use of anticoagulation. Nitrous oxide may be administered for labor analgesia while using appropriate personal protective equipment. Intravenous remifentanil patient-controlled analgesia should be used with caution in patients with respiratory depression. Liberal use of neuraxial labor analgesia may reduce the need for emergency general anesthesia which results in aerosolization. Short courses of non-steroidal anti-inflammatory drugs can be administered for postpartum analgesia, but opioids should be used with caution due to the risk of respiratory depression. For mechanically ventilated pregnant patients, neuromuscular blockade should be used for the shortest duration possible and reversal agents should be available on hand if delivery is imminent. To date, dexamethasone is the only proven and recommended experimental treatment for pregnant patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen. Although hydroxycholoroquine, lopinavir/ritonavir and remdesivir may be used during pregnancy and lactation within the context of clinical trials, data from non-pregnant populations have not shown benefit. The role of monoclonal antibodies (tocilizumab), immunomodulators (tacrolimus), interferon, inhaled nitric oxide and convalescent plasma in pregnancy and lactation needs further evaluation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Core competencies in critical care for general medical practitioners in South Africa: A Delphi study.

Background: Despite a high burden of disease that requires critical care services, there are a limited number of intensivists in South Africa (SA). Medical practitioners at district and regional public sector hospitals frequently manage critically ill patients in the absence of intensivists, despite these medical practitioners having had minimal exposure to critical care during their undergraduate training. Objectives: To identify core competencies in critical care for medical practitioners who provide critical care services at public sector hospitals in SA where intensivists are not available to direct patient management. Methods: A preliminary list of core competencies in critical care was compiled. Thereafter, 13 national and international experts were requested to achieve consensus on a final list of core competencies that are required for critical care by medical practitioners, using a modified Delphi process. Results: A final list of 153 core competencies in critical care was identified. Conclusion: The core competencies identified by this study could assist in developing training programmes for medical practitioners to improve the quality of critical care services provided at district and regional hospitals in SA. Contribution of the study: The study provides consensus on a list of core competencies in critical care that non-intensivist medical practitioners managing critically ill patients in healthcare settings in South Africa, especially where intensivists are not readily available, should have. The list can form the core content of training programmes aimed at improving critical care competence of general medical practitioners, and in this way hopefully improve the overall outcomes of critically ill patients in South Africa.

Epidemiology of influenza-associated hospitalization in adults, Toronto, 2007/8.

The purpose of this investigation was to identify when diagnostic testing and empirical antiviral therapy should be considered for adult patients requiring hospitalization during influenza seasons. During the 2007/8 influenza season, six acute care hospitals in the Greater Toronto Area participated in active surveillance for laboratory-confirmed influenza requiring hospitalization. Nasopharyngeal (NP) swabs were obtained from patients presenting with acute respiratory or cardiac illness, or with febrile illness without clear non-respiratory etiology. Predictors of influenza were analyzed by multivariable logistic regression analysis and likelihoods of influenza infection in various patient groups were calculated. Two hundred and eighty of 3,917 patients were found to have influenza. Thirty-five percent of patients with influenza presented with a triage temperature >or=38.0 degrees C, 80% had respiratory symptoms in the emergency department, and 76% were >or=65 years old. Multivariable analysis revealed a triage temperature >or=38.0 degrees C (odds ratio [OR] 3.1; 95% confidence interval [CI] 2.3-4.1), the presence of respiratory symptoms (OR 1.7; 95% CI 1.2-2.4), admission diagnosis of respiratory infection (OR 1.8; 95% CI 1.3-2.4), admission diagnosis of exacerbation of chronic obstructive pulmonary disease (COPD)/asthma or respiratory failure (OR 2.3; 95% CI 1.6-3.4), and admission in peak influenza weeks (OR 4.2; 95% CI 3.1-5.7) as independent predictors of influenza. The likelihood of influenza exceeded 15% in patients with respiratory infection or exacerbation of COPD/asthma if the triage temperature was >or=38.0 degrees C or if they were admitted in the peak weeks during the influenza season. During influenza season, diagnostic testing and empiric antiviral therapy should be considered in patients requiring hospitalization if respiratory infection or exacerbation of COPD/asthma are suspected and if either the triage temperature is >or=38.0 degrees C or admission is during the weeks of peak influenza activity.

Mechanical ventilation in critically-ill pregnant women: a case series.

BACKGROUND: Approximately 0.1-0.2% of pregnancies are complicated by respiratory failure requiring mechanical ventilatory support, but few data exist to inform clinical management. This study aimed to characterize current practice and the effect of delivery on respiratory function. METHODS: A retrospective review was performed of pregnant women who received mechanical ventilation for more than 24h, from four intensive care units in institutions with large-volume obstetric units. RESULTS: Data were collected from 29 patients with a mean gestation at intensive care unit admission of 25.3 ± 6 weeks. Tidal volumes were 7.7 ± 1.7 mL/kg predicted body weight. Estimated respiratory system compliance was reduced, but was higher in four patients ventilated for neurological conditions without lung disease. Three maternal and three neonatal deaths occurred. Ten patients delivered while on ventilatory support: one spontaneous delivery, four for obstetric indications and five for worsening maternal condition. Following delivery of these 10 patients, three demonstrated a greater than 50% decrease in oxygenation index and five a greater than 50% increase in compliance. No characteristics identified which patients may benefit from delivery. CONCLUSIONS: Review of current practice in four centers suggests that mechanical ventilation in pregnant patients follows usual guidelines applicable to non-pregnant patients. Delivery was associated with modest improvement in maternal respiratory function in some patients. Any potential benefit of delivery in improving maternal physiology must be weighed against the stress of delivery. The risks of premature birth for the fetus must be weighed against continued exposure to maternal hypoxemia and hypotension.

Determinants of near fatality in acute severe asthma.

PURPOSE: The data extrapolated from cases of acute severe asthma that narrowly miss being fatal may prove valuable in the identification of the factors implicated in mortality. The purpose of this study was, therefore, to identify determinants of near fatality in patients with acute severe asthma. PATIENTS AND METHODS: We studied 81 patients with acute severe asthma in whom mechanical ventilation was required. Near fatality was defined as the occurrence of respiratory arrest and/or coma necessitating emergency tracheal intubation and resuscitation. In the cases that were not regarded as near fatal, tracheal intubation was performed electively because of deteriorating arterial blood gas values and/or the anticipation of exhaustion. Various continuous and categorical variables were compared in these two groups of patients. Patients with a hyperacute attack (period from onset of attack to mechanical ventilation less than 3 hours) were specifically sought and studied to determine the impact of such a course on near fatality. RESULTS: The "attack duration" (period from onset of attack to mechanical ventilation) was an important determinant of near fatality and of the subsequent clinical course. It was shorter in the group with a near-fatal episode (p < 0.03), and hyperacute attacks were uniformly near fatal. The attack duration correlated positively with the duration of the requirement for mechanical ventilation (p < 0.01). A longer attack duration was associated with an increased likelihood of the occurrence of major atelectasis (p < 0.01). There was no evidence of a relationship between near fatality and the side effects of bronchodilators as regards hypokalemia, arrhythmias, or cardiotoxicity. There was evidence of considerable under-treatment in the patient population as a whole, particularly in regard to the use of corticosteroids. CONCLUSIONS: A short attack duration is associated with an increased risk of near fatality in acute severe asthma. This is particularly evident in hyperacute attacks. Hyperacute attacks resolve rapidly once bronchodilator therapy has been instituted, suggesting that smooth muscle spasm is the predominant pathogenetic mechanism. The importance of routine anti-inflammatory therapy in mild to moderate asthma requires re-emphasis but, in addition, all patients should be provided with, and educated in the use of, bronchodilator rescue therapy, which should be available at all times. Despite current trends, the use of regular, prophylactic bronchodilator therapy in strict conjunction with anti-inflammatory agents may still be indicated. There is little evidence in the present data obtained from near-fatal cases to support the concept that cardiotoxicity related to bronchodilators contributes significantly to mortality from asthma.

Trepopnea due to interatrial shunt following lung resection.

Dyspnea and platypnea following pneumonectomy have been reported as a result of right-to-left interatrial shunt. We report on a case of trepopnea with marked positional arterial oxygen desaturation following right middle and lower lobectomy. A similar mechanism was found, with right-to-left interatrial shunting occurring predominantly in the right lateral position. Surgical repair corrected the clinical and physiologic abnormalities.

Acute reversible cardiomyopathy associated with the systemic inflammatory response syndrome.

In the absence of ischemic heart disease, severe acute reversible myocardial dysfunction is uncommon, with sepsis most often being implicated in the ICU. We report a 38-year-old woman who developed profound transient myocardial depression due to nonseptic systemic inflammatory response syndrome caused by a necrotic kidney. Hemodynamic parameters and echocardiographic findings improved dramatically following nephrectomy. Other causes of acute myocardial suppression, including electrolyte abnormalities, drugs, catecholamine excess, and endocrine disease were excluded.

Management of acute respiratory failure due to pulmonary edema with nasal positive pressure support.

The management of patients with respiratory failure from cardiogenic pulmonary edema may require intubation and mechanical ventilation. This provides both ventilatory assistance as well as the beneficial hemodynamic effects of positive intrathoracic pressure. As the need for ventilation is usually short term, noninvasive ventilatory support may be adequate. We report the use of biphasic positive airway pressure by nasal mask (BiPAP system) to successfully manage two patients with respiratory failure due to pulmonary edema.

Safety and efficacy of a sustained inflation for alveolar recruitment in adults with respiratory failure.

OBJECTIVE: To assess the safety and efficacy of a sustained inflation, used as a lung volume recruitment maneuver in ventilated patients with hypoxemic respiratory failure. DESIGN: Prospective data collection as part of a quality assurance program following introduction of a lung volume recruitment guideline in the intensive care unit. SETTING: Academic medical-surgical critical care unit. PATIENTS: Hypoxemic patients with bilateral pulmonary infiltrates. Patients with chronic obstructive pulmonary disease, pulmonary barotrauma and hemodynamic instability were excluded. INTERVENTIONS: A sustained inflation using a pressure of 30 to 45 cmH2O was applied for 20 s. The pressure was determined as the lesser of 45 cmH2O or the peak pressure while ventilated at a tidal volume of 12 ml/kg. Intra-arterial blood pressure and pulse oximetry were monitored continuously. MEASUREMENTS AND RESULTS: Significant improvement in oxygenation occurred in the majority of patients within 10 min. The mean oxygen saturation improved from 86.9 +/- 5.5 to 94.3 +/- 2.3% (p < 0.01). No significant adverse effects were noted: hypotension and mild oxygen desaturation occurred in some patients during the 20-s inflation, reversing rapidly after inflation was terminated. No barotrauma occurred. CONCLUSIONS: A sustained inflation is a safe, clinically applicable method of lung volume recruitment which improves oxygenation in selected patients and may have a role in ventilatory management.

Rapid pulmonary phospholipid accumulation induced by intravenous amiodarone.

Amiodarone causes accumulation of phospholipids in lung alveolar cells, and this phospholipidosis invariably is present when amiodarone pulmonary toxicity is recognized. This effect has usually been demonstrated in patients following several months of therapy. The authors report the occurrence of pulmonary phospholipidosis, diagnosed by bronchoalveolar lavage, six days after commencing intravenous amiodarone therapy.

Predictors of mortality in patients undergoing autologous hematopoietic cell transplantation admitted to the intensive care unit.

Between January 2001 and July 2006, 1013 patients received autologous hematopoietic cell transplants (AHCT) at Canada's largest transplant center. In this retrospective cohort study of AHCT patients admitted to the intensive care unit (ICU), we describe the outcomes following ICU admission and the variables measured in the first 24 h of ICU admission associated with overall ICU mortality. Results indicate a 3.3% ICU admission rate (n=34) with 13 deaths (1% overall mortality rate, 38% in ICU mortality rate). The worst outcome was in AL amyloid patients of whom 28% were admitted to the ICU, with an ICU mortality rate of 55%. The Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) score in the first 24 h were statistically associated with mortality by univariate analysis. Other variables measured at 24 h and associated with ICU mortality included multiorgan failure, mechanical ventilation, inotropic support >4 h and Gram-negative sepsis. Our data indicate that ICU admission in the autotransplant population is rare and that it is influenced by underlying diagnosis, with AL amyloid patients having the highest risk. Our observations may assist clinical decision-making regarding the continuation of intensive care delivered 24 h after ICU admission.

Quantification and assessment of viability of Pneumocystis carinii organisms by flow cytometry.

Analysis of drug efficacy in animal models of Pneumocystis carinii pneumonia requires an accurate method of quantification of organisms, as well as a means of assessing viability. Lung homogenates were prepared from a colony of athymic nude F344 rats experiencing a spontaneous outbreak of P. carinii pneumonia. With the fluorescent nucleic acid stain propidium iodide, flow cytometric analysis was able to quantify P. carinii cysts and trophozoites reproducibly. As this stain is excluded by living cells, this method was also used to assess the viability of organisms. Application of this technique to analysis of bronchoalveolar lavage specimens was demonstrated.

Handheld computers in critical care.

BACKGROUND: Computing technology has the potential to improve health care management but is often underutilized. Handheld computers are versatile and relatively inexpensive, bringing the benefits of computers to the bedside. We evaluated the role of this technology for managing patient data and accessing medical reference information, in an academic intensive-care unit (ICU). METHODS: Palm III series handheld devices were given to the ICU team, each installed with medical reference information, schedules, and contact numbers. Users underwent a 1-hour training session introducing the hardware and software. Various patient data management applications were assessed during the study period. Qualitative assessment of the benefits, drawbacks, and suggestions was performed by an independent company, using focus groups. An objective comparison between a paper and electronic handheld textbook was achieved using clinical scenario tests. RESULTS: During the 6-month study period, the 20 physicians and 6 paramedical staff who used the handheld devices found them convenient and functional but suggested more comprehensive training and improved search facilities. Comparison of the handheld computer with the conventional paper text revealed equivalence. Access to computerized patient information improved communication, particularly with regard to long-stay patients, but changes to the software and the process were suggested. CONCLUSIONS: The introduction of this technology was well received despite differences in users' familiarity with the devices. Handheld computers have potential in the ICU, but systems need to be developed specifically for the critical-care environment.

Critical care management of the obstetric patient.

PURPOSE: To review a series of critically ill obstetric patients admitted to a general intensive care unit in a Canadian centre, to assess the spectrum of diseases, interventions required and outcome. METHODS: A retrospective chart review was performed of obstetric patients admitted to the intensive care unit of an academic hospital with a high-risk obstetric service, during a five-year period. Data obtained included the admission diagnosis, ICU course and outcome. Daily APACHE II and TISS scores were recorded. RESULTS: Sixty-five obstetric patients, representing 0.26% of deliveries in this hospital, were admitted to the ICU during the study period. All had received prenatal care. Admission diagnoses included obstetric (71%) and non-obstetric (29%) complications. The mean APACHE II score was 6.8 +/- 4.2 and mean TISS score was 24 +/- 8.1. Twenty-seven patients (42%) required mechanical ventilation. No maternal mortality occurred and the perinatal mortality rate was 11%. CONCLUSIONS: A small proportion of obstetric patients develop complications requiring ICU admission. The outcome in this study was excellent, in contrast to that reported in other published studies with similar ICU admission rates. The universal availability of prenatal care may be an important factor in the outcome of this group of patients. The lack of a specific severity of illness scoring system for the pregnant patient makes comparison of case series difficult.

Utility of routine chest radiographs in a medical-surgical intensive care unit: a quality assurance survey.

OBJECTIVE: To determine the utility of routine chest radiographs (CXRs) in clinical decision-making in the intensive care unit (ICU). DESIGN: A prospective evaluation of CXRs performed in the ICU for a period of 6 months. A questionnaire was completed for each CXR performed, addressing the indication for the radiograph, whether it changed the patient's management, and how it did so. SETTING: A 14-bed medical-surgical ICU in a university-affiliated, tertiary care hospital. PATIENTS: A total of 645 CXRs were analyzed in 97 medical patients and 205 CXRs were analyzed in 101 surgical patients. RESULTS: Of the 645 CXRs performed in the medical patients, 127 (19.7%) led to one or more management changes. In the 66 surgical patients with an ICU stay <48 hours, 15.4% of routine CXRs changed management. In 35 surgical patients with an ICU stay > or = 48 hours, 26% of the 100 routine films changed management. In both the medical and surgical patients, the majority of changes were related to an adjustment of a medical device. CONCLUSIONS: Routine CXRs have some value in guiding management decisions in the ICU. Daily CXRs may not, however, be necessary for all patients.

Anaemia, iron-related measurements and erythropoietin levels in untreated patients with active leprosy.

The mechanisms responsible for anaemia in leprosy were studied prior to the institution of therapy in 56 patients with active disease. Haematological indices, iron-related measurements, inflammatory markers and erythropoietin levels were assessed, with bone-marrow studies being performed on anaemic patients. Anaemia was more common in the patients with lepromatous leprosy (85.7%) than it was in the rest of the group (19%). The lepromatous group exhibited the disordered iron transport of the anaemia of chronic disorders in that they had a significantly lower mean serum iron level (P less than 0.05), and a mildly raised serum ferritin concentration. Anaemic lepromatous patients also showed a blunted erythropoietin response compared with controls with non-inflammatory anaemia. A subgroup of five anaemic subjects displayed apparently adequate transport of iron to the erythroid marrow (normal percentage transferrin saturations and appropriate sideroblast counts) and the blunted erythropoietin response appeared to be the dominant factor in the pathogenesis of their anaemia. Analysis of inflammatory markers revealed that while the erythrocyte sedimentation rate was very high in the lepromatous subjects, there was no concomitant rise in C-reactive protein concentration. This suggests the presence of a disordered cytokine-mediated acute phase response in the condition.

Prospective trial of high-frequency oscillation in adults with acute respiratory distress syndrome.

OBJECTIVE: To evaluate the safety and efficacy of high-frequency oscillatory ventilation (HFOV) in adult patients with the acute respiratory distress syndrome (ARDS) and oxygenation failure. DESIGN: Prospective, clinical study. SETTING: Intensive care and burn units of two university teaching hospitals. PATIENTS: Twenty-four adults (10 females, 14 males, aged 48.5 +/- 15.2 yrs, Acute Physiology and Chronic Health Evaluation II score 21.5 +/- 6.9) with ARDS (lung injury score 3.4 +/- 0.6, Pao2/Fio2 98.8 +/- 39.0 mm Hg, and oxygenation index 32.5 +/- 19.6) who met one of the following criteria: Pao2 < or =65 mm Hg with Fio2 > or =0.6, or plateau pressure > or =35 cm H2O. INTERVENTIONS: HFOV was initiated in patients with ARDS after varying periods of conventional ventilation (CV). Mean airway pressure (Paw) was initially set 5 cm H2O greater than Paw during CV, and was subsequently titrated to maintain oxygen saturation between 88% and 93% and Fio2 < or =0.60. MEASUREMENTS AND MAIN RESULTS: Fio2, Paw, pressure amplitude of oscillation, frequency, blood pressure, heart rate, and arterial blood gases were monitored during the transition from CV to HFOV, and every 8 hrs thereafter for 72 hrs. In 16 patients who had pulmonary artery catheters in place, cardiac hemodynamics were recorded at the same time intervals. Throughout the HFOV trial, Paw was significantly higher than that applied during CV. Within 8 hrs of HFOV application, and for the duration of the trial, Fio2 and Paco2 were lower, and Pao2/Fio2 was higher than baseline values during CV. Significant changes in hemodynamic variables following HFOV initiation included an increase in pulmonary artery occlusion pressure (at 8 and 40 hrs) and central venous pressure (at 16 and 40 hrs), and a reduction in cardiac output throughout the course of the study. There were no significant changes in systemic or pulmonary pressure associated with initiation and maintenance of HFOV. Complications occurring during HFOV included pneumothorax in two patients and desiccation of secretions in one patient. Survival at 30 days was 33%, with survivors having been mechanically ventilated for fewer days before institution of HFOV compared with nonsurvivors (1.6 +/- 1.2 vs. 7.8 +/- 5.8 days; p =.001). CONCLUSIONS: These findings suggest that HFOV has beneficial effects on oxygenation and ventilation, and may be a safe and effective rescue therapy for patients with severe oxygenation failure. In addition, early institution of HFOV may be advantageous.