Obesity and Weaning from Mechanical Ventilation-An Exploratory Study.

INTRODUCTION: Obesity is associated with increased risk of hypercapnic respiratory failure, prolonged duration on mechanical ventilation, and extended weaning periods. OBJECTIVE: Pilot study to determine whether morbidly obese adult tracheotomized subjects (body mass index [BMI] ⩾ 40) can be more efficiently weaned from the ventilator by optimizing their positive end-expiratory pressure (PEEP) using either an esophageal balloon or the best achieved static effective compliance. METHODS: We randomly assigned 25 morbidly obese adult tracheotomized subjects (median [interquartile range] BMI 53.4 [26.4]; range 40.4-113.8) to 1 of 2 methods of setting PEEP; using either titration guided by esophageal balloon to overcome negative transpulmonary pressure (Ptp) (goal Ptp 0-5 cmH2O) (ESO group) or titration to maximize static effective lung compliance (Cstat group). Our outcomes of interest were number of subjects weaned by day 30 and time to wean. RESULTS: At day 30, there was no significant difference in percentage of subjects weaned. 8/13 subjects (62%) in the ESO Group were weaned vs. 9/12(75%) in the Cstat Group (P = 0.67). Among the 17 subjects who weaned, median time to ventilator liberation was significantly shorter in the ESO group: 3.5 days vs Cstat group 14 days (P = .01). Optimal PEEP in the ESO and Cstat groups was similar (ESO mean ± SD = 26.5 ± 5.7 cmH2O and Cstat 24.2 ± 7 cmH2O (P = .38). CONCLUSIONS: Optimization of PEEP using esophageal balloon to achieve positive transpulmonary pressure did not change the proportion of patients weaned. Among patients who weaned, use of the esophageal balloon resulted in faster liberation from mechanical ventilation. There were no adverse consequences of the high PEEP (mean 25.4; range 13-37 cmH2O) used in our study. The study was approved by the Institutional Review Board at our institution (UMCIRB#10-0343) and registered with clinicaltrials.gov (NCT02323009).

Can a collaborative subspecialty antimicrobial stewardship intervention have lasting effects?

OBJECTIVE: We previously demonstrated the benefit of direct, daily collaboration between infectious disease (ID) and critical care practitioners (CCP) on guideline adherence and antibiotic use in the medical intensive care unit (MICU). In this post-intervention review, we sought to establish whether the effect on antibiotic use and guideline adherence was sustainable. DESIGN: A retrospective review of 87 patients, admitted to the 24-bed MICU, was done 3 (n = 45) and 6 months (n = 42) after the intervention. MEASUREMENTS: Data included demographics, severity indicators, admitting pathology, infectious diagnosis, clinical outcomes [mechanical ventilation days (MVD) and MICU length of stay (LOS), antibiotic days of therapy (DOT), in-hospital mortality], and antibiotic appropriateness based on current guidelines. RESULTS: In the 3-month (3-PI) and 6-month post-intervention (6-PI), there were no significant differences in the APACHE II score, MVD, LOS, DOT, or total antibiotic use at 3 (p = 0.59) and 6-PI (p = 0.87). There was no change in the mean use of extended-spectrum penicillins, cephalosporin, and carbapenems. While there were significant differences in vancomycin usage at 3-PI [3.1 DOT vs. 4.3 DOT (p = 0.007)], this finding was not seen after 6 months [3.1 DOT vs. 3.4 DOT (p = 0.08)]. When compared to the intervention period, the inappropriateness of antibiotic use at 3 (p = 1.00) and 6-PI (p = 0.30) did not change significantly. CONCLUSIONS: There were no significant differences in either total antibiotic use or inappropriate antibiotic use at the 6-PI time period. Continuous, daily, direct collaboration between ID and CCP, once implemented, can have lasting effects even at 6 months after the interaction has been discontinued.

Impact of regular collaboration between infectious diseases and critical care practitioners on antimicrobial utilization and patient outcome.

OBJECTIVE: Antimicrobial stewardship programs have been shown to help reduce the use of unnecessary antimicrobial agents in the hospital setting. To date, there has been very little data focusing on high-use areas, such as the medical ICU. A prospective intervention was done to assess guideline compliance, antimicrobial expenditure, and healthcare cost when an infectious disease fellow interacts regularly with the medical ICU team. DESIGN: A 3-month retrospective chart review was followed by a 3-month prospective intervention the following year. Two hundred forty-six total charts were reviewed to assess generally accepted guideline compliance, demographics, and microbiologic results. SETTING: Twenty-four-bed medical ICU at an 861-bed tertiary care, university teaching hospital in North Carolina. SUBJECTS: Patients receiving antibiotics in the medical ICU. INTERVENTION: During the intervention period, the infectious disease fellow reviewed the charts, including physician notes and microbiology data, and discussed antimicrobial use with the medical ICU team. MEASUREMENTS AND MAIN RESULTS: Antimicrobial use, treatment duration, Acute Physiology and Chronic Health Evaluation II scores, length of stay, mechanical ventilation days, and mortality rates were compared during the two periods. RESULTS: No baseline statistically significant differences in the two groups were noted (i.e., age, gender, race, or Acute Physiology and Chronic Healthcare Evaluation II scores). Indications for antibiotics included healthcare-associated (53%) and community-acquired pneumonias (17%). Significant reductions were seen in extended-spectrum penicillins (p=0.0080), carbapenems (p=0.0013), vancomycin (p=0.0040), and metronidazole (p=0.0004) following the intervention. Antimicrobial modification led to an increase in narrow-spectrum penicillins (p=0.0322). The intervention group had a significantly lower rate of treatments that did not correspond to guidelines (p<0.0001). There was a reduction in mechanical ventilation days (p=0.0053), length of stay (p=0.0188), and hospital mortality (p=0.0367). The annual calculated healthcare savings was $89,944 in early antibiotic cessation alone. CONCLUSION: Active communication with an infectious disease practitioner can significantly reduce medical ICU antibiotic overuse by earlier modification or cessation of antibiotics without increasing mortality. This in turn can reduce healthcare costs, foster prodigious education, and strengthen relations between the subspecialties.

The infusion of opioids during terminal withdrawal of mechanical ventilation in the medical intensive care unit.

CONTEXT: Most deaths in intensive care units occur after limitation or withdrawal of life-sustaining therapies. Often these patients require opioids to assuage suffering; yet, little has been documented concerning their use in the medical intensive care unit. OBJECTIVES: To determine the dose and factors influencing the use of opioids in patients undergoing terminal withdrawal of mechanical ventilation in this setting. METHODS: Data were prospectively collected from 74 consecutive patients expected to die soon after extubation. The doses of morphine, effect on time to death, and relation of dose to diagnostic categories were analyzed. RESULTS: The mean (±standard deviation) dose of morphine given to patients during the last hour of mechanical ventilation was 5.3mg/hour. Patients dying after extubation received 10.6 mg/hour just before death. Immediately before extubation, the dose correlated directly with chronic medical opioid use and sepsis with respiratory failure and inversely with coma after cardiopulmonary resuscitation or a primary neurological event. After terminal extubation, the final morphine dose correlated directly with the presence of sepsis with respiratory failure and chronic pulmonary disease. The mean time to death after terminal extubation was 152.7 ± 229.5 minutes without correlation with premorbid diagnoses. After extubation, each 1mg/hour increment of morphine infused during the last hour of life was associated with a delay of death by 7.9 minutes (P = 0.011). CONCLUSION: Premorbid conditions may influence the dose of morphine given to patients undergoing terminal withdrawal of mechanical ventilation. Higher doses of morphine are associated with a longer time to death.

Low levels of NF-κB/p65 mark anergic CD4+ T cells and correlate with disease severity in sarcoidosis.

T lymphocytes from patients with sarcoidosis respond weakly when stimulated with mitogen or antigen. However, the mechanisms responsible for this anergy are not fully understood. Here, we investigated the protein levels of nuclear transcription factor NF-κB (p50, p65, and p105), IκBα (inhibitor of NF-κB), T-cell receptor (TCR) CD3ζ-chain, tyrosine kinase p56(LCK), and nuclear factor of activated T cells c2 (NF-ATc2) in peripheral blood CD4(+) T cells from patients with sarcoidosis. Baseline expression of p65 in these lymphocytes was reduced in 50% of patients. The reduced levels of p65 in sarcoid CD4(+) T cells concurred with decreased levels of p50, p105, CD3ζ, p56(LCK), IκBα, and NF-ATc2. Polyclonal stimulation of NF-κB-deficient sarcoid T cells resulted in reduced expression of CD69 and CD154, decreased proliferation, and cytokine (i.e., interleukin 2 [IL-2] and gamma interferon [IFN-γ]) production. The clinical significance of these findings is suggested by the association between low p65 levels and the development of more severe and active sarcoidosis. Although correlative, our results support a model in which multiple intrinsic signaling defects contribute to peripheral T-cell anergy and the persistence of chronic inflammation in sarcoidosis.

Pancreatic pseudocyst rupture into the portal vein.

A patient with a pancreatic pseudocyst rupture into the portal vein with a resultant noninfectious systemic inflammatory response syndrome and subsequent portal vein thrombosis diagnosed by computed tomography and ultrasonography is reported. A review of the existing English literature on this rare complication is also provided.

The public's attitude and perception concerning witnessed cardiopulmonary resuscitation.

OBJECTIVE: For healthcare providers, witnessed cardiopulmonary resuscitation (CPR) is controversial. However, little is known about the public's stance on this issue. This study was performed to develop insight concerning the general public's thoughts about witnessed CPR. DESIGN: A random telephone survey. SETTING: Rural southwest Pennsylvania. SUBJECTS: Four hundred and eight respondents, >/=18 yrs old, residing in Conemaugh Health System's Memorial Medical Center's service area. INTERVENTIONS: : Demographic information was gathered concerning the respondents, who rated their level of agreement with questions concerning witnessed resuscitation. MEASUREMENTS AND MAIN RESULTS: Of the respondents, 49.3% desired to be present while CPR is performed on a loved one. Respondents desiring CPR were more apt to believe that significant others have a right to be present during CPR (p = .010) and want significant others present with them while undergoing CPR than those declining CPR (p < .001). Respondents desiring CPR felt more strongly that the presence of family or friends during CPR would benefit the patient (p = .022). The desire to be present in the room with a loved one during CPR did not reach statistical significance (p = .275) between the two groups, nor did the belief that that being present would benefit family and friends (p = .093). Of the respondents, 43% believed that the physician should have the most authority in making decisions about witnessed resuscitation, 40% believed that the patient should have the most authority, and 17% believed that family and friends should have the most authority (p < .001). Those who believed that family and friends should have the most authority were more favorable toward witnessed resuscitation than were those who believed that either the patient or the physician should have the most authority. CONCLUSIONS: This study offers insights into the public's attitude concerning witnessed resuscitation. A large segment of the population desires the presence of significant others during CPR and conversely want to be with loved ones during CPR. Further studies should investigate the public's attitude in more diverse settings, and formal programs to accommodate those who wish to remain together during CPR should be developed.

Severe hypersensitivity pneumonitis associated with anagrelide.

OBJECTIVE: To report a case of severe life-threatening hypersensitivity pneumonitis temporally associated with the use of anagrelide in a patient with myeloproliferative disorder. CASE SUMMARY: A 60-year-old white woman with chronic myeloid leukemia who had been treated with hydroxyurea for 7 years was offered anagrelide to control thrombocytosis. She developed severe hypersensitivity pneumonitis soon after the drug was initiated and required intubation and mechanical ventilation. A high-resolution computed tomography scan of the chest demonstrated extensive multifocal ground glass attenuation and patchy alveolar consolidation involving both lungs. Bronchoalveolar lavage revealed a preponderance of lymphocytes, suggesting hypersensitivity phenomenon, but was otherwise negative for malignancy and other causes of interstitial pneumonitis. An objective causality assessment revealed that an adverse drug event was probable. Discontinuation of anagrelide and hydroxyurea, and institution of corticosteroid therapy resulted in dramatic improvement. DISCUSSION: To our knowledge, this is the first case report of severe hypersensitivity pneumonitis closely related to anagrelide therapy. Pulmonary infiltrates have rarely been noted in patients treated with anagrelide. Anagrelide does not depress white blood cell production, causes mild anemia, and is devoid of the leukemogenic potential characteristic of radioactive phosphorus and other alkylating agents. Common adverse effects to anagrelide include headache, nausea, diarrhea, peripheral edema, and palpitations. Frank congestive heart failure and cardiomyopathy have occurred in a small number of patients, but severe pulmonary adverse effects have not emerged as a frequent problem. CONCLUSIONS: Vigilance is advised in patients who develop dyspnea while taking anagrelide and hydroxyurea. Healthcare providers need to be aware of the possibility of the development of serious life-threatening hypersensitivity pneumonitis. These patients may benefit from serial chest X-rays, pulmonary function testing, and echocardiography.