Noninvasive Monitoring of Cardiac Output During Weaning From Mechanical Ventilation: A Pilot Study.

BACKGROUND: Cardiac dysfunction is one of many causes for unsuccessful weaning from mechanical ventilation. Although cardiac dysfunction can be detected via direct measurement of cardiac output during weaning, available methods are not feasible. OBJECTIVE: To investigate the role of noninvasive monitoring of cardiac output during weaning and determine if a relationship exists between serial measurements during the spontaneous breathing trial and weaning outcomes. METHODS: A prospective, observational study was conducted in the intensive care unit at a university-affiliated teaching hospital. The sample consisted of patients intubated for more than 24 hours who were being weaned off of mechanical ventilation according to a validated weaning protocol. Before the first spontaneous breathing trial, a noninvasive cardiac output monitor was connected to the ventilator circuit. Measurements were made before, at the beginning of, and at the end of the trial. RESULTS: Among the 85 patients tested, baseline cardiac output was similar (P = .93) for those in whom the first trial was successful (mean [SD], 5.7 [2.1] L/min) and those in whom the trial was unsuccessful (5.6 [1.8] L/ min). Unlike patients with unsuccessful trials, patients with successful trials were able to augment their cardiac output from baseline. Mean cardiac output increased to 7.1 (SD, 3.1) L/min for patients in whom weaning was successful and to 6.2 (SD, 2.3) L/min for those in whom weaning was unsuccessful (P = .001). CONCLUSION: A noninvasive method of monitoring cardiac output can be easily applied while patients are being weaned off of mechanical ventilation.

Efficacy and safety of early dexmedetomidine during noninvasive ventilation for patients with acute respiratory failure: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Successful application of noninvasive ventilation (NIV) for acute respiratory failure (ARF) requires patient cooperation and comfort. The efficacy and safety of early IV dexmedetomidine when added to protocolized, as-needed IV midazolam and fentanyl remain unclear. METHODS: Adults with ARF and within 8 h of starting NIV were randomized to receive IV dexmedetomidine (0.2 µg/kg/h titrated every 30 min to 0.7 µg/kg/h to maintain a Sedation-Agitation Scale [SAS] score of 3 to 4) or placebo in a double-blind fashion up to 72 h, until NIV was stopped for ≥ 2 h, or until intubation. Patients with agitation (SAS ≥ 5) or pain (visual analog scale ≥ 5 of 10 cm) 15 min after each dexmedetomidine and placebo increase could receive IV midazolam 0.5 to 1.0 mg or IV fentanyl 25 to 50 µg, respectively, at a minimum interval of every 3 h. RESULTS: The dexmedetomidine (n = 16) and placebo (n = 17) groups were similar at baseline. Use of early dexmedetomidine did not improve NIV tolerance (score, 1 of 4; OR, 1.44; 95% CI, 0.44-4.70; P = .54) nor, vs. placebo, led to a greater median (interquartile range) percent time either tolerating NIV (99% [61%-100%] vs. 67% [40%-100%], P = .56) or remaining at the desired sedation level (SAS score = 3 or 4, 100% [86%-100%] vs. 100% [100%-100%], P = .28], or fewer intubations (P = .79). Although use of dexmedetomidine was associated with a greater duration of NIV vs placebo (37 [16-72] vs. 12 [4-22] h, P = .03), the total ventilation duration (NIV + invasive) was similar (3.3 [2-4] days vs. 3.8 [2-5] days, P = .52). More patients receiving dexmedetomidine had one or more episodes of deep sedation vs placebo (SAS ≤ 2, 25% vs. 0%, P = .04). Use of midazolam (P = .40) and episodes of either severe bradycardia (heart rate ≤ 50 beats/min, P = .18) or hypotension (systolic BP ≤ 90 mm Hg, P = .64) were similar. CONCLUSIONS: Initiating dexmedetomidine soon after NIV initiation in patients with ARF neither improves NIV tolerance nor helps to maintain sedation at a desired goal. Randomized, multicenter trials targeting patients with initial intolerance are needed to further elucidate the role for dexmedetomidine in this population.

An update on pulmonary complications of hematopoietic stem cell transplantation.

The indications for hematopoietic stem cell transplantation (HSCT) continue to expand. However, the risk for pulmonary complications post-HSCT continues to be high. Early recognition and treatment of pulmonary complications may improve outcomes. This is an overview of diagnosis, manifestations, and treatment of the most common infectious and noninfectious pulmonary complications post-HSCT. Knowing the patient's timeframe post-HSCT (preengraftment, postengraftment, late), type of HSCT (allogeneic vs autologous), radiographic findings, and clinical presentation can help to differentiate between the many pulmonary complications. This article will also address pretransplantation evaluation and infectious and noninfectious complications in the patient post-HSCT. While mortality post-HSCT continues to improve, respiratory failure continues to be the leading cause of ICU admissions for patients who have undergone HSCT. Mechanical ventilation is a predictor of poor outcomes in these patients, and further research is needed regarding their critical care management, treatment options for noninfectious pulmonary complications, and mortality prediction models posttransplantation.

Asthma associations in children attending a museum of science.

We explored the relative strength of environmental and social factors associated with pediatric asthma in middle class families and considered the efficacy of recruitment for an educational study at a science museum. Eligibility criteria were having a child aged 4-12 and English fluency. Our questionnaire included information on demographics, home environment, medical history, and environmental toxicant exposures. Statistically significant associations were found for: child's age (t = -2.46; p = 0.014), allergies (OR = 11.5; 95%CI = 5.9-22.5), maternal asthma (OR = 2.2; 95%CI = 1.2-3.9), parents' education level (OR = 0.5; 95%CI = 0.3-0.9), family income (OR = 2.4; 95%CI = 1.1-5.5), water damage at home (OR = 2.5; 95%CI = 1.1-5.5), stuffed animals in bedroom (OR = 0.4; 95%CI = 0.2-0.7), hospitalization within a week after birth (OR = 3.2; 95%CI = 1.4-7.0), diagnosis of pneumonia (OR = 2.8; 95%CI = 1.4-5.9), and multiple colds in a year (OR = 2.9; 95%CI = 1.5-5.7). Several other associations approached statistical significance, including African American race (OR = 3.3; 95%CI = 1.0-10.7), vitamin D supplement directive (OR = 0.2; 95%CI = 0.02-1.2), mice in the home (OR = 0.5, 95%CI = 0.2-1.1), and cockroaches in the home (OR = 4.3; CI = 0.8-21.6). In logistic regression, age, parents' education, allergies, mold allergies, hospitalization after birth, stuffed animals in the bedroom, vitamin D supplement directive, and water damage in the home were all significant independent predictors of asthma. The urban science museum was a low-resource approach to address the relative importance of risk factors in this population.

Dihydropteroate synthase mutations in Pneumocystis pneumonia: impact of applying different definitions of prophylaxis, mortality endpoints and mutant in a single cohort.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations are well-reported. Although sulfa prophylaxis generally is associated with DHPS mutant infection, whether mutant infection is associated with poorer clinical outcomes is less clear. The differing definitions of sulfa prophylaxis and the different mortality endpoints used in these studies may be one explanation for the conflicting study results. Applying different definitions of prophylaxis, mortality endpoints and DHPS mutant to 301 HIV-infected patients with Pneumocystis pneumonia, we demonstrate that prophylaxis, irrespective of definition, increased the risk of infection with pure mutant (any prophylaxis: AOR 4.00, 95% CI: 1.83-8.76, P < 0.001) but not mixed genotypes (any prophylaxis: AOR 0.78, 95% CI: 0.26-2.36, P = 0.65). However, infection with mutant DHPS, irrespective of definition, was not associated with increased mortality (all-cause or PCP death) at the three time-intervals examined (all P > 0.05). Future studies should standardize key variables associated with DHPS mutant infection as well as examine DHPS mutant subtypes (pure mutant vs. mixed infections) - perhaps even individual DHPS mutant genotypes - so that data can be pooled to better address this issue.

Infrared imaging of nitric oxide-mediated blood flow in human sickle cell disease.

Vascular dysfunction is an important pathophysiologic manifestation of sickle cell disease (SCD), a condition that increases risk of pulmonary hypertension and stroke. We hypothesized that infrared (IR) imaging would detect changes in cutaneous bloodflow reflective of vascular function. We performed IR imaging and conventional strain gauge plethysmography in twenty-five adults with SCD at baseline and during intra-arterial infusions of an endothelium-dependent vasodilator acetylcholine (ACh), an endothelium-independent vasodilator sodium nitroprusside (SNP), and a NOS inhibitor L-NMMA. Skin temperature measured by IR imaging increased in a dose-dependent manner to graded infusions of ACh (+1.1°C, p<0.0001) and SNP (+0.9°C, p<0.0001), and correlated with dose-dependent increases in forearm blood flow (ACh: +19.9 mL/min/100 mL, p<0.0001; r(s)=0.57, p=0.003; SNP: +8.6 mL/min/100 mL, p<0.0001; r=0.70, p=0.0002). Although IR measurement of skin temperature accurately reflected agonist-induced increases in blood flow, it was less sensitive to decreases in blood flow caused by NOS inhibition. Baseline forearm skin temperature measured by IR imaging correlated significantly with baseline forearm blood flow (31.8±0.2°C, 6.0±0.4 mL/min/100 mL; r=0.58, p=0.003), and appeared to represent a novel biomarker of vascular function. It predicted a blunted blood flow response to SNP (r=-0.61, p=0.002), and was independently associated with a marker of pulmonary artery pressure, as well as hemoglobin level, diastolic blood pressure, homocysteine, and cholesterol (R(2)=0.84, p<0.0001 for the model). IR imaging of agonist-stimulated cutaneous blood flow represents a less cumbersome alternative to plethysmography methodology. Measurement of baseline skin temperature by IR imaging may be a useful new marker of vascular risk in adults with SCD.

Impact of a national propofol shortage on duration of mechanical ventilation at an academic medical center.

OBJECTIVE: To measure the impact of a national propofol shortage on the duration of mechanical ventilation. DESIGN: Before-after study. SETTING: Three, noncardiac surgery, adult intensive care units at a 320-bed academic medical center. PATIENTS: Consecutive patients requiring mechanical ventilation ≥48 hrs, administered a continuously infused sedative ≥24 hrs, extubated, and successfully discharged from the intensive care unit were compared between before (December 1, 2008 to May 31, 2009) and after (December 1, 2009, to May 31, 2010) a propofol shortage. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sedation drug use and common factors affecting time on mechanical ventilation were collected and if found either to differ significantly (p ≤ .10) between the two groups or to have an unadjusted significant association (p ≤ .10) with time on mechanical ventilation were included in a multivariable model. The unadjusted analyses revealed that the median (interquartile range) duration of mechanical ventilation increased from 6.7 (9.8; n = 153) to 9.6 (9.5; n = 128) days (p = .02). Fewer after-group patients received ≥24 hrs of continuously infused propofol (94% vs. 15%, p < .0001); more received ≥24 hrs of continuously infused lorazepam (7% vs. 15%, p = .037) and midazolam (30% vs. 81%, p < .0001). Compared with the before group, the after group was younger, had a higher admission Acute Physiology and Chronic Health Evaluation II score, was more likely to be admitted by a surgical service, have acute alcohol withdrawal, and be managed with pressure-controlled ventilation as the primary mode of mechanical ventilation. Of these five factors, only the Acute Physiology and Chronic Health Evaluation II score, admission service, and use of a pressure-controlled ventilation affected duration of mechanical ventilation across both groups. Although a regression model revealed that Acute Physiology and Chronic Health Evaluation II score (p < .0001), admission by a medical service (p = .009), and use of pressure-controlled ventilation (p = .02) each affected duration of mechanical ventilation in both groups, inclusion in either the before- or after-propofol shortage groups (i.e., high vs. low use of propofol) did not affect duration of mechanical ventilation (p = .35). CONCLUSIONS: An 84% decrease in propofol use in the adult intensive care units at our academic institution as a result of a national shortage did not affect duration of mechanical ventilation.

Survival for patients With HIV admitted to the ICU continues to improve in the current era of combination antiretroviral therapy.

BACKGROUND: The combination antiretroviral therapy (ART) era (1996 to the present) has been associated with improved survival among HIV-infected outpatients, but ICU data from 2000 to the present are limited. METHODS: We conducted a retrospective study of HIV-infected adults who had been admitted to the ICU at San Francisco General Hospital (from 2000 to 2004). The primary outcome was survival to hospital discharge. RESULTS: During the 5-year study period, there were 311 ICU admissions for 281 patients. Respiratory failure remained the most common indication for ICU admission (42% overall), but the proportion of patients with respiratory failure decreased each year from 52 to 34% (p = 0.02). Hospital survival ratios significantly increased during the 5-year period (p = 0.001). ART use at ICU admission was not associated with survival, but it was associated with higher CD4 cell counts, lower plasma HIV RNA levels, higher serum albumin levels, and lower proportions with AIDS-associated ICU admission diagnoses and with Pneumocystis pneumonia. In a multivariate analysis, a higher serum albumin level (adjusted odds ratio [AOR], 2.08; 95% confidence interval [CI], 1.41 to 3.06; p = 0.002) and the absence of mechanical ventilation (AOR, 6.11; 95% CI, 2.73 to 13.72; p < 0.001) were associated with survival. CONCLUSIONS: In this sixth in a series of consecutive studies started in 1981, we found that the epidemiology of ICU admission diagnoses continues to change. Our study also found that survival for critically ill HIV-infected patients continues to improve in the current era of ART. Although ART use was not associated with survival, it was associated with predictors that were associated with survival in a multivariate analysis.

Proteomic identification of altered apolipoprotein patterns in pulmonary hypertension and vasculopathy of sickle cell disease.

Pulmonary arterial hypertension (PAH) is emerging as a major complication and independent risk factor for death among adults with sickle cell disease (SCD). Using surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS), we searched for biomarkers of PAH in plasma specimens from 27 homozygous sickle cell anemia (HbSS) patients with PAH and 28 without PAH. In PAH patients, analysis consistently showed lower abundance of a 28.1-kDa peak (P < .001), identified by high-resolution mass spectrometry as the oxidant-scavenging protein apolipoprotein A-I (apoA-I), which correlated with clinical assays of apoA-I (r = .58, P < .001) and high-density lipoprotein (HDL) levels (r = .50, P = .001). Consistent with endothelial dysfunction that may mediate this effect in PAH, HbSS patients with lower apoA-I levels also displayed impaired vasodilatory responses to acetylcholine (mean +/- SEM, 189% +/- 34% [n = 13] vs 339% +/- 51% [n = 13], P < .001). As a group, patients with SCD demonstrated significantly lower apoA-I levels than African-American control subjects. The PAH cohort was further characterized by high levels of apolipoproteins A-II and B and serum amyloid A, and low levels of haptoglobin dimers and plasminogen. These results imply a relationship of apolipoproteins to the development of PAH vasculopathy in SCD, potentially involving an unexpected mechanistic parallel to atherosclerosis, another proliferative vasculopathy.