Critical care management of pulmonary arterial hypertension in pregnancy: the pre-, peri- and post-partum stages.

The mortality rate of pulmonary hypertension in pregnancy is 25%-56%. Pulmonary arterial hypertension is the highest incidence among this group, especially in young women. Despite clear recommendation of pregnancy avoidance, certain groups of patients are initially diagnosed during the gestational age step into the third trimester. While the presence of right ventricular failure in early gestation is usually trivial, it can be more severe in the late trimester. Current evidence shows no consensus in the management and serious precautions for each stage of the pre-, peri- and post-partum periods of this specific group. Pulmonary hypertension-targeted drugs, mode of delivery, type of anesthesia, and some avoidances should be planned among a multidisciplinary team to enhance maternal and fetal survival opportunities. Sudden circulatory collapse from cardiac decompensation during the peri- and post-partum phases is detrimental, and mechanical support such as extracorporeal membrane oxygenation should be considered for mitigating hemodynamics and extending cardiac recovery time. Our review aims to explain the pathophysiology of pulmonary arterial hypertension and summarize the current evidence for critical management and precautions in each stage of pregnancy.

Multimodality treatment in immunocompromised patients with severe COVID-19: the role of IL-6 inhibitor, intravenous immunoglobulin, and haemoperfusion.

Cytokine release syndrome (CRS) is known to be associated with severe coronavirus disease 2019 (COVID-19). Multiple anti-inflammatory therapies such as tocilizumab, corticosteroids, intravenous immunoglobulin (IVIG), and haemoadsorption or haemoperfusion have been used to combat this life-threatening condition. However, immunocompromised hosts are often omitted from research studies, and knowledge on the clinical efficacy of these therapies in immunocompromised patients is therefore limited. We report two cases of immunocompromised patients with severe COVID-19-related CRS requiring mechanical ventilation who were treated with multimodality treatment consisting of tocilizumab, IVIG, and haemoperfusion. Within 48 h, both patients showed clinical improvement with PaO2:FiO2 ratio and haemodynamic stability. Both survived to discharge. There were no adverse events following these therapies. In conclusion, combined therapeutic modalities, possibly tailored to individual inflammatory profiles, are promising treatment for severe COVID-19 infection in the immunocompromised host. Timely administration of adjunctive therapies that alleviate overwhelming inflammation may provide the best outcome.

Fulminant respiratory muscle paralysis, an expanding clinical spectrum of mitochondrial A3243G tRNALeu mutation.

Mitochondrial disease is a group of rare disorders, caused by mitochondrial dysfunction. They are usually the result of mutations of either mitochondrial DNA or nuclear DNA. A3243G transition in the tRNALeu is one the most frequent mutations of the mitochondrial DNA. Phenotypic expression of this mutation varies. The most well-recognized phenotype is Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Isolated myopathy with respiratory muscle weakness in this mutation has been rarely documented. The authors reported a 20-year-old Asian female presenting with a fulminant hypoventilatory respiratory failure with mild weakness of the limbs. Electrophysiologic study showed evidences of myopathy. Restrictive physiology of the lungs was demonstrated by pulmonary function test. Subsarcolemmal accumulation of mitochondria was demonstrated by Gomori trichrome and succinate dehydrogenase stains. Genetic study revealed the A3243G mutation in mitochondrial DNA in peripheral blood Isolated mitochondrial myopathy severely affecting respiratory muscles may be considered as an uncommon clinical spectrum of A3243G mitochondrial disease.

Prevalence of obstructive lung disease in HIV population: a cross sectional study.

BACKGROUND: Observational studies have suggested an association between HIV infection and emphysema. AIMS: The primary aim of this study was to estimate the prevalence of obstructive lung disease in HIV-infected patients seen in an outpatient infectious disease clinic. The secondary aim was to estimate the prevalence of Obstructive Lung Disease (OLD) in smokers and non smokers in this population. METHODS: This was a prospective cross-sectional study. Consecutive patients who were seen for routine HIV care underwent spirometry and answered the St. George's Respiratory Questionnaire (SGRQ). Further, we collected information from the charts on demographics, co-morbidities, CD4 cell count, and HIV viral load (current, baseline, etc). RESULTS: This study included 98 HIV-infected patients with mean age of 45 years, (SD: 11) and 84% male. They were seen from November 2008 to May 2009 at Thomas Jefferson University in Philadelphia. According to established criteria, spirometry results were classified as normal in 69% and obstructive in 16.3%. Among those who never smoked, the prevalence of obstructive lung disease on spirometry was 13.6%. The prevalence of obstruction in HIV patients with a history of smoking was 18.5%. Current and ever smokers comprised 21.4% and 55% of the patients respectively. The mean SGRQ total score was 7. The mean SGRQ score in active smokers was 17 and 15 in those subjects with a prior history of smoking. The mean SGRQ score among patients with obstruction in spiromerty was 27.7 in patients with obstruction on spirometry. CONCLUSION: This urban population of HIV-infected persons has a relatively high prevalence of obstructive lung disease as assessed by spirometry. Furthermore, the high prevalence of obstructive lung disease in never smokers may suggest a possible association between HIV infection and emphysema. In addition the SGRQ total score was comparatively higher in patients with obstruction on spirometry. Our data suggests that potentially all patients with HIV should be screened a for OLD.

Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis.

BACKGROUND: Recent observational studies suggest that bleeding from stress ulceration is extremely uncommon in intensive care unit patients. Furthermore, the risk of bleeding may not be altered by the use of acid suppressive therapy. Early enteral tube feeding (initiated within 48 hrs of intensive care unit admission) may account for this observation. Stress ulcer prophylaxis may, however, increase the risk of hospital-acquired pneumonia and Clostridia difficile infection. OBJECTIVE: A systematic review of the literature to determine the benefit and risks of stress ulcer prophylaxis and the moderating effect of enteral nutrition. DATA SOURCES: MEDLINE, Embase, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. STUDY SELECTION: Randomized, controlled studies that evaluated the association between stress ulcer prophylaxis and gastrointestinal bleeding. We included only those studies that compared a histamine-2 receptor blocker with a placebo. DATA EXTRACTION: Data were abstracted on study design, study size, study setting, patient population, the histamine-2 receptor blocker and dosage used, the incidence of clinically significant gastrointestinal bleeding, hospital-acquired pneumonia, mortality, and the use of enteral nutrition. DATA SYNTHESIS: Seventeen studies (which enrolled 1836 patients) met the inclusion criteria. Patients received adequate enteral nutrition in three of the studies. Overall, stress ulcer prophylaxis with a histamine-2 receptor blocker reduced the risk of gastrointestinal bleeding (odds ratio 0.47; 95% confidence interval, 0.29-0.76; p < .002; I = 44%); however, the treatment effect was noted only in the subgroup of patients who did not receive enteral nutrition. In those patients who were fed enterally, stress ulcer prophylaxis did not alter the risk of gastrointestinal bleeding (odds ratio 1.26; 95% confidence interval, 0.43-3.7). Overall histamine-2 receptor blockers did not increase the risk of hospital-acquired pneumonia (odds ratio 1.53; 95% confidence interval, 0.89-2.61; p = .12; I = 41%); however, this complication was increased in the subgroup of patients who were fed enterally (odds ratio 2.81; 95% confidence interval, 1.20-6.56; p = .02; I = 0%). Overall, stress ulcer prophylaxis had no effect on hospital mortality (odds ratio 1.03; 95% confidence interval, 0.78-1.37; p = .82). The hospital mortality was, however, higher in those studies (n = 2) in which patients were fed enterally and received a histamine-2 receptor blocker (odds ratio 1.89; 95% confidence interval, 1.04-3.44; p = .04, I = 0%). Sensitivity analysis and meta-regression demonstrated no relationship between the treatment effect (risk of gastrointestinal bleeding) and the classification used to define gastrointestinal bleeding, the Jadad quality score nor the year the study was reported. CONCLUSIONS: The results of this meta-analysis suggest that, in those patients receiving enteral nutrition, stress ulcer prophylaxis may not be required and, indeed, such therapy may increase the risk of pneumonia and death. However, because no clinical study has prospectively tested the influence of enteral nutrition on the risk of stress ulcer prophylaxis, our findings should be considered exploratory and interpreted with some caution.

Association between time of admission to the ICU and mortality: a systematic review and metaanalysis.

BACKGROUND: The organizational and staffing structure of an ICU influences the outcome of critically ill and injured patients. A change in the ICU staffing structure frequently occurs at nighttime and on weekends (off-hours). We postulated that patients who are admitted to an ICU during off hours may be at an increased risk of death. METHODS: We performed a systematic review of the literature to assess whether admission to an ICU during off-hours is associated with an increased mortality. We selected studies that evaluated the association between time of admission to the ICU and mortality, with adjustment for severity of disease. We excluded studies that included pediatric and non-ICU patients. Study characteristics extracted included date of publication, study design, country where study was done, study population, time factor (weekend or night shift), severity adjustment tool, and outcome. RESULTS: Ten cohort studies met our inclusion criteria; eight of these studies evaluated nighttime admissions, whereas six studies evaluated weekend admissions. The pooled analysis demonstrated that nighttime admission was not associated with an increased mortality (odds ratio [OR], 1.0 [95% CI, 0.87-1.17]; P = .956); however, patients admitted over the weekend had a significant increase in the adjusted risk of death (OR, 1.08 [95% CI, 1.04-1.13]; P < .001). Significant heterogeneity was found in the studies that evaluated nighttime admissions. CONCLUSIONS: Whereas patients admitted to an ICU over the weekend appear to be at an increased risk of death, nighttime admissions were not associated with an increased mortality. The lower level of staffing and intensity of care provided by many hospitals over the weekend may account for this finding. The heterogeneity noted between studies evaluating nighttime admissions likely reflects the diverse organizational structure of the hospitals and ICUs where these studies were carried out.

Influence of malignancy on the decision to withhold or withdraw life-sustaining therapy in critically ill patients.

PURPOSE: To evaluate the influence of malignancy on the decision to limit life-sustaining therapy in the intensive care unit (ICU). METHODS: At the day of patients' admission to the ICU, we prospectively collected information on demographics, acute physiology and chronic health evaluation (APACHE) II score, and features related to malignancy. We retrospectively collected information on in-hospital survival and decision to withhold or withdraw life-sustaining treatment. RESULTS: This study included 122 adult critically ill patients. After adjusting for age and APACHE II score, patients with malignancy had 3.02 (95% CI 1.19 to 7.62) higher odds of having life-sustaining therapy withdrawn or withheld as compared to patients without active malignancy. CONCLUSION: Our study showed that critically ill patients with malignancy are more likely to have their life-sustaining therapy withheld or withdrawn than those without malignancy after adjusting for severity of disease. This finding may be related to a perception that critically ill patients with malignancy have worse prognosis as compared with those without malignancy.

Bovine blood and neuromuscular paralysis as a bridge to recovery in a patient with severe autoimmune hemolytic anemia.

Hemoglobin solutions have several advantages as substitutes for erythrocyte transfusions. They have a prolonged shelf life, do not require cross-matching, are associated with few transfusion reactions, and are effective in delivering oxygen to the tissues. Despite the potential clinical utility of these solutions, they have not achieved widespread use. HbOC-201 (Hemopure, Biopure, Cambridge, MA, USA) is a bovine hemoglobin solution that has been FDA approved for compassionate use in Jehovah's witness patients requiring transfusions. Here we report a case of a patient with hemoglobin H disease who developed a severe life-threatening mixed warm and cold antibody mediated autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) who was successfully treated with HbOC-201 as an adjunct to blood transfusion.