Ventilatory Parameters Measured After One Week of Mechanical Ventilation and Survival in COVID-19-Related ARDS.

BACKGROUND: Ventilatory parameters measured soon after initiation of mechanical ventilation have limited ability to predict outcome of COVID-19-related ARDS. We hypothesized that ventilatory parameters measured after one week of mechanical ventilation might differ between survivors and non-survivors. METHODS: One hundred twenty-seven subjects with COVID-related ARDS had gas exchange and lung mechanics assessed on the day of intubation and one week later. The main parameters of interest were PaO2 /FIO2 , ventilatory ratio (VR), respiratory system compliance (CRS), and a composite score that was calculated as (PaO2 /FIO2 /100) × CRS/VR. The primary outcome was death in the ICU. RESULTS: Of the 127 subjects, 42 (33%) died in the ICU and 85 (67%) were successfully extubated. On the day of intubation, PaO2 /FIO2 , CRS, and composite score of survivors and non-survivors were similar, but survivors had a lower VR. At one week, as compared to survivors, non-survivors had a significantly higher VR (2.04 ± 0.76 vs 1.60 ± 0.43, P < .001), lower CRS (27.4 ± 6.4 mL/cm H2O vs 32.4 ± 9.3 mL/cm H2O, P = .002), and lower composite score (20.6 ± 11.9 vs 34.5 ± 18.6, P < .001), with no statistically significant difference in PaO2 /FIO2 (137 ± 49 vs 155 ± 48, P = .08). CONCLUSIONS: In subjects with COVID ARDS, parameters that reflect dead space (VR), lung mechanics (CRS), and a combined score that included PaO2 /FIO2 , VR, and CRS differed between survivors and non-survivors after one week of mechanical ventilation but with considerable overlap of values between survivors and non-survivors.

Naloxone-associated pulmonary edema following recreational opioid overdose.

OBJECTIVE: Describe a series of patients who developed naloxone-associated pulmonary edema after recreational opioid use. DESIGN: Single center retrospective case series of patients who developed pulmonary edema following the prehospital administration of naloxone. SETTING: Academic, urban safety-net hospital. PATIENTS: Adults with recreational opioid overdose who developed naloxone-associated pulmonary edema, defined as the acute onset of respiratory distress, hypoxemia, and radiographic pulmonary edema after naloxone administration for opioid intoxication, provided that gas exchange and chest imaging rapidly improved and pulmonary aspiration of gastric contents was not clinically suspected. MEASUREMENTS AND MAIN RESULTS: Ten adults (median age 23 years, 90% male) met our case definition for naloxone-associated pulmonary edema. Implicated opioids were heroin in 8 patients and methadone and oxycodone in 1 patient each. The median total dose of naloxone was 4.25 mg (interquartile range [IQR] 3.3-9.8) prior to the onset of clinically-apparent pulmonary edema. Seven patients received invasive mechanical ventilation for a median of two days (IQR 0.8-5), one of whom received veno-venous extracorporeal membrane oxygenation support, and all survived to hospital discharge. CONCLUSIONS: Severe acute pulmonary edema may follow naloxone administration after recreational opioid overdose. Acute care clinicians should be aware of this potentially life-threatening adverse effect of naloxone.

Characteristics and outcomes of critically ill patients with severe hyperammonemia.

PURPOSE: To determine the etiology and outcomes of critically ill patients with severe hyperammonemia. MATERIALS AND METHODS: Retrospective observational study of adults (18 years or older) admitted to a MICU from 2007 to 2016 who had a serum ammonia level >180 µmol/L (3 times the upper limit of normal). RESULTS: The 78 patients (45 male, 32 female) had a median age of 52 (interquartile range [IQR] 46-58) years. Hyperammonemia occurred most often with acute-on-chronic liver failure (ACLF) (49 %) or decompensated cirrhosis (27 %) and less often as a consequence of prior gastric bypass (9%), acute hepatic failure (6%), or valproic acid (3%). Median serum ammonia level was 201 µmol/L (IQR 126-265, range 18-736) on admission, with peak value of 245 µmol/L (IQR 205-336, range 185-842). Fifty (64%) patients died during the hospitalization. Cerebral edema was documented in 8 (10%) patients, only one of whom survived. Six of the 8 patients with cerebral edema had hyperammonemia related to ACLF, giving an incidence of 14% in this subset of patients. Neither mortality nor cerebral edema was associated with peak ammonia level. CONCLUSIONS: Critically ill patients with severe hyperammonemia have a high mortality rate and are at risk of developing cerebral edema.

Lack of Benefit of Heliox During Mechanical Ventilation of Subjects With Severe Air-Flow Obstruction.

BACKGROUND: The value of heliox (helium-oxygen mixture) for patients with severe air-flow obstruction is uncertain. The purpose of this study was to determine whether heliox could reduce the degree of hyperinflation and hypercapnia in mechanically ventilated patients with severe air-flow obstruction. METHODS: This was a single-center, prospective observational study conducted in a medical ICU of an academic medical center. We assessed the impact of heliox (65-70% helium, 30-35% oxygen) on airway pressures and arterial blood gases of 13 subjects undergoing mechanical ventilation for severe asthma (n = 8) or exacerbation of COPD (n = 5). RESULTS: As compared with ventilation with air-O2, heliox resulted in a reduction in peak airway pressure (54.1 ± 12.6 cm H2O vs 47.9 ± 10.8 cm H2O, P < .001) and PaCO2 (64.3 ± 14.9 mm Hg vs 62.3 + 15.1 mm Hg, P = .01). In contrast, there was no change in plateau pressure (25.3 ± 5.5 cm H2O vs 25.8 ± 5.6 cm H2O, P = .14) or total PEEP (13.4 ± 3.8 cm H2O vs 13.3 ± 4.1 cm H2O, P = .79) in response to heliox. CONCLUSIONS: In mechanically ventilated subjects with severe air-flow obstruction, administration of heliox had no effect on indices of dynamic hyperinflation (plateau pressure and total PEEP) and resulted in only a small reduction in PaCO2 .

Measurement of Femoral Vein Diameter by Ultrasound to Estimate Central Venous Pressure.

RATIONALE: Central venous pressure (CVP) can be estimated by ultrasound of the inferior vena cava (IVC), but imaging the IVC is sometimes challenging. The femoral vein is easily imaged by ultrasound and might therefore provide an alternate target for estimating CVP. OBJECTIVES: To assess femoral vein diameter (FVD) measured by ultrasound imaging for estimating CVP. METHODS: We prospectively measured CVP and FVD in 97 patients. Receiver operating characteristic curves were used to assess the ability of FVD to predict specific CVP values: less than 10 mm Hg, less than 8 mm Hg (low CVP), and greater than 12 mm Hg (high CVP). Interobserver variability of FVD measurement was assessed in 20 patients. MEASUREMENTS AND MAIN RESULTS: There was moderate correlation between FVD and CVP (r = 0.66, P < 0.001). FVD less than or equal to 0.8 cm was the best predictor of CVP < 10 mm Hg, with an area under the curve (AUC) of 0.894 and a 95% confidence interval (CI) of 0.82 to 0.97. FVD less than or equal to 0.7 cm performed best for predicting low CVP (AUC = 0.97; 95% CI, 0.94-0.99) and FVD greater than or equal to 1.0 cm for high CVP (AUC = 0.80; 95% CI, 0.72-0.89). However, FVD greater than or equal to 1.2 cm had the greatest specificity (94%) for high CVP. Interobserver variability in FVD measurements was 8.3 ± 7.2%. CONCLUSIONS: The results of this exploratory study suggest that the accuracy of FVD measured by ultrasound imaging for estimating CVP is comparable to that which has been reported for ultrasound measurement of IVC diameter. FVD may provide an alternative approach when the IVC is difficult to image. Additional studies on other cohorts of patients are warranted to validate our proposed FVD cutoff values for predicting low and high CVP.

Point-of-care ultrasound to estimate central venous pressure: a comparison of three techniques.

OBJECTIVE: To determine the most accurate predictor of central venous pressure among three point-of-care venous ultrasound techniques. DESIGN: Cross-sectional study. SETTING: Medical ICU in an academic medical center. PATIENTS: Convenience sample of 67 spontaneously breathing patients who had an intrathoracic central venous catheter to allow measurement of central venous pressure. INTERVENTION: Measurement of the internal jugular vein height to width ratio (aspect ratio), the inferior vena cava diameter, and the percent collapse of the inferior vena cava with inspiration (collapsibility index) by ultrasound. MEASUREMENTS AND MAIN RESULTS: Complete data for analysis were available in 65 patients, as the inferior vena cava could not be visualized in two patients. A central venous pressure of 10 mm Hg was chosen a priori as a clinically significant cutoff. The range of central venous pressure values was 1-23 mm Hg with a median value of 7 mm Hg. The maximal inferior vena cava diameter correlated moderately with central venous pressure (R = 0.58), whereas the inferior vena cava collapsibility index and the internal jugular vein aspect ratio showed poor correlation (R = 0.16 and 0.21, respectively). The area under the receiver operating characteristics curve (area under the curve) to discriminate a low central venous pressure (< 10 mm Hg) was 0.91 for inferior vena cava diameter (95% confidence interval 0.84-0.98), which was significantly higher than the internal jugular vein aspect ratio (area under the curve 0.76; 95% confidence interval 0.65-0.89) or the inferior vena cava collapsibility index (area under the curve 0.66; 95% confidence interval 0.51-0.80) (p = 0.0001). An inferior vena cava diameter < 2 cm predicted a central venous pressure < 10 mm Hg with a sensitivity of 85% (95% confidence interval 69% to 94%), specificity of 81% (95% confidence interval 60% to 93%), and positive predictive value of 87% (95% confidence interval 71% to 95%). Inferior vena cava collapsibility index was not an independent predictor of central venous pressure after adjusting for inferior vena cava diameter in a multiple linear regression model. CONCLUSION: Among spontaneously breathing patients largely without vasopressor support, the maximal inferior vena cava diameter is a more robust estimate of central venous pressure than the inferior vena cava collapsibility index or the internal jugular vein aspect ratio.

Use of expiratory change in bladder pressure to assess expiratory muscle activity in patients with large respiratory excursions in central venous pressure.

BACKGROUND: Expiratory muscle activity may cause the end-expiratory central venous pressure (CVP) to greatly overestimate right atrial transmural pressure. METHODS: We recorded CVP and expiratory change in intra-abdominal pressure (ΔIAP) in 39 patients who had a respiratory excursion in CVP from end-expiration to end-inspiration (CVP(ee)-CVP(ei)) ≥ 8 mmHg. Uncorrected CVP was measured at end-expiration, and corrected CVP was calculated as uncorrected CVP-ΔIAP. In 13 patients measurements were repeated during relaxed breathing. RESULTS: The CVP(ee)-CVP(ei) was 15.2 ± 6.3 mmHg (range 8-34 mmHg), and ΔIAP was 7.4 ± 6.0 mmHg (range 0-30 mmHg). Uncorrected CVP was 18.3 ± 6.1 mmHg, and corrected CVP was 10.9 ± 3.9 mmHg. There was a significant positive correlation between CVP(ee)-CVP(ei) and ΔIAP (r = 0.814). However, some patients with a large CVP(ee)-CVP(ei) had negligible ΔIAP. In a subset of 13 patients with active expiration who had a relaxed CVP tracing available for comparison, the difference between uncorrected CVP and relaxed CVP was much greater than the difference between corrected CVP and relaxed CVP (7.3 ± 3.0 vs. 1.1 ± 0.7 mmHg, p < 0.001). CONCLUSION: Patients with large respiratory excursions in CVP often have significant expiratory muscle activity that will cause their CVP to overestimate transmural right atrial pressure. The magnitude of expiratory muscle activity can be assessed by measuring ΔIAP. Subtracting ΔIAP from the end-expiratory CVP usually provides a reasonable estimate of the CVP that would be obtained if exhalation were passive.

Assessment of left ventricular function by intensivists using hand-held echocardiography.

BACKGROUND: Bedside transthoracic echocardiography (TTE) provides rapid and noninvasive hemodynamic assessment of critically ill patients but is limited by the immediate availability of experienced sonographers and cardiologists. METHODS: Forty-four patients in the medical ICU underwent near-simultaneous limited TTE performed by intensivists with minimal training in echocardiography, and a formal TTE that was performed by certified sonographers and was interpreted by experienced echocardiographers. Intensivists, blinded to the patient's diagnosis and the results of the formal TTE, were asked to determine whether left ventricular (LV) function was grossly normal or abnormal and to place LV function into one of the following three categories: 1, normal; 2, mildly to moderately decreased; and 3, severely decreased. RESULTS: Using the formal TTE as the "gold standard," intensivists correctly identified normal LV function in 22 of 24 cases (92%) and abnormal LV function in 16 of 20 cases (80%). The kappa statistic for the agreement between intensivist and echocardiographer for any abnormality in LV function was 0.72 (95% confidence interval [CI], 0.52 to 0.93; p < 0.001). Intensivists correctly placed LV function into one of three categories in 36 of 44 cases (82%); in 6 of the 8 cases that were misclassified, the error involved an overestimation of LV function. The kappa statistic for agreement between the intensivist and echocardiographer with regard to placement into one of three categories of LV function was 0.68 (95% CI, 0.48 to 0.88; p < 0.001). CONCLUSIONS: Intensivists were able to estimate LV function with reasonable accuracy using a hand-held unit in the ICU, despite having undergone minimal training in image acquisition and interpretation.

Severe weakness complicating status asthmaticus despite minimal duration of neuromuscular paralysis.

OBJECTIVE: Mechanically ventilated patients with status asthmaticus who undergo prolonged paralysis are at risk for severe weakness due to myopathy. In the mid-1990s, we changed our usual method of achieving tolerance of ventilatory support in asthmatic patients from continuous paralysis to deep sedation. This study examines the impact of this change in practice on the development of clinically significant weakness in status asthmaticus. DESIGN AND SETTING: Retrospective cohort study in university-affiliated county hospital. PATIENTS: Mechanically ventilated asthmatic patients seen before (n = 96) and after (n = 74) a clinical practice change in 1995 that markedly restricted use of paralytics. RESULTS: The duration of neuromuscular paralysis declined sharply after 1995 (23.7 +/- 42.2 vs. 1.8 +/- 4.0 h, P < 0.001), but this was not associated with a significant difference in the incidence of weakness (21 vs. 14%, P = 0.23). Within the post-1995 cohort, there was no significant difference in the duration of paralysis for weak and non-weak patients (3.5 +/- 6.2 vs. 1.5 +/- 3.5 h, P = 0.10). However, weak patients had a much longer duration of mechanical ventilation than did patients without weakness (11.9 +/- 3.6 vs. 1.9 +/- 1.8 days, P < 0.001). CONCLUSION: Mechanically ventilated patients with status asthmaticus who are immobilized for prolonged periods of time by deep sedation remain at risk for clinically significant weakness.

Use of bladder pressure to correct for the effect of expiratory muscle activity on central venous pressure.

OBJECTIVE: To assess whether subtracting the expiratory change in intra-abdominal (bladder) pressure (Delta IAP) from central venous pressure (CVP) provides a reliable estimate of transmural CVP in spontaneously breathing patients with expiratory muscle activity. DESIGN AND SETTING: Prospective observational study in a medical ICU. PATIENTS: Twenty-four spontaneously breathing patients with central venous and bladder catheters: 18 with no clinical evidence of active expiration (group 1) and 6 with active expiration (group 2). INTERVENTIONS: Patients in group 1 were coached to change their breathing pattern to one of active expiration for several breaths; those in group 2 were asked to sip water through a straw to briefly interrupt active expiration. MEASUREMENTS AND RESULTS: During active expiration end-expiratory CVP (uncorrected CVP) and Delta IAP were measured; Delta IAP was subtracted from uncorrected CVP to obtain corrected CVP. End-expiratory CVP during relaxed breathing (best CVP) was assumed to represent the best estimate of transmural CVP. The absolute difference between corrected CVP and best CVP was much less than the difference between uncorrected CVP and best CVP (2.3+/-2.0 vs. 12.5+/-4.7 mmHg). CONCLUSIONS: In patients with active expiration, subtracting Delta IAP from end-expiratory CVP yields a more reliable (and lower) estimate of transmural CVP than does the uncorrected CVP value.

Effect of prolongation of expiratory time on dynamic hyperinflation in mechanically ventilated patients with severe asthma.

OBJECTIVE: To assess the effect of a decrease in respiratory rate on dynamic hyperinflation, as determined by changes in plateau airway pressure, in patients with status asthmaticus whose baseline minute ventilation approximated 10 L/min. DESIGN: Observational descriptive study. SETTING: Medical intensive care unit. PATIENTS: Twelve patients with severe asthma mechanically ventilated in the assist control mode with a tidal volume of 613 +/- 100 mL and an inspiratory flow rate of 79 +/- 4 L/min. INTERVENTIONS: A decrease in respiratory rate from 18 to 12 and 6 breaths/min. MEASUREMENTS AND MAIN RESULTS: Plateau airway pressure decreased by approximately 2 cm H2O (25.4 +/- 2.8 vs. 23.3 +/- 2.6 cm H2O, p <.01) when respiratory rate was decreased from 18 to 12 breaths/min (increase in expiratory time 1.7 secs) and by a similar amount (23.3 +/- 2.6 vs. 21.3 +/- 2.9 cm H2O, p <.01) when respiratory rate was decreased from 12 to 6 breaths/min (increase in expiratory time 5 secs). Peak airway pressure was similar at the three respiratory rates (66.8 +/- 8.7 vs. 66.4 +/- 9.5 vs. 67.8 +/- 11.1 cm H2O at 18, 12, and 6 breaths/min, respectively). End-expiratory flow rates (n = 7) were 61.4 +/- 12.6, 38.6 +/- 4.5, and 23.1 +/- 5.8 mL/sec at respiratory rates of 18, 12, and 6 breaths/min, respectively. CONCLUSIONS: Prolongation of expiratory time decreases dynamic hyperinflation in patients with status asthmaticus, as evidenced by a reduction in plateau airway pressure, but the magnitude of this effect is relatively modest when baseline minute ventilation is < or = 10 L/min, because of the low end-expiratory flow rates. Since flow progressively decreases throughout expiration, the reduction in dynamic hyperinflation resulting from a given prolongation of expiratory time will depend on the baseline respiratory rate (i.e., less reduction in dynamic hyperinflation at a lower respiratory rate). Changes in peak airway pressure may not always reflect the changes in dynamic hyperinflation that result from prolongation of expiratory time.

Overestimation of pulmonary artery occlusion pressure in pulmonary hypertension due to partial occlusion.

OBJECTIVE: To evaluate partial occlusion in patients with pulmonary hypertension with regard to a) the degree to which it leads to overestimation of pulmonary artery occlusion pressure (Ppao) and b) identification of factors that could enhance its recognition. DESIGN: Observational descriptive study. SETTING: Medical intensive care unit. PATIENTS: Fourteen patients with pulmonary hypertension and an increased pulmonary artery diastolic pressure (Ppad) - Ppao gradient (> or = 10 mm Hg). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Ppao was recorded during partial occlusion (partial Ppao) and after catheter repositioning to obtain a lower, more accurate value (best Ppao). The error due to partial occlusion, defined as the difference between the partial Ppao and the best Ppao, was 13 +/- 5 mm Hg (range, 6-21 mm Hg). The previously widened Ppad - Ppao gradient invariably narrowed during partial occlusion and then increased by 13 +/- 5 mm Hg (range, 5-23) during the best Ppao measurement. There was a moderate correlation between the error due to partial occlusion (partial Ppao - best Ppao) and both the mean pulmonary artery pressure (r =.77, <.01) and the Ppad - Ppao gradient (r =.79, <.01). CONCLUSIONS: Partial occlusion in patients with pulmonary hypertension may lead to significant overestimation of the Ppao and should be suspected when there is a substantial increase in the Ppao without a concomitant increase in the Ppad, as reflected by a marked narrowing of a previously widened Ppad - Ppao gradient.

Neuromuscular disorders in the intensive care unit.

Neuromuscular disorders encountered in the ICU can be categorized as muscular diseases that lead to ICU admission and those that are acquired in the ICU. This article discusses three neuromuscular disorders can lead to ICU admission and have a putative immune-mediated pathogenesis: the Guillian-Barré syndrome, myasthenia gravis, and dermatomyositis/polymyositis. It also reviews critical care polyneuropathy and ICU acquired myopathy, two disorders that, alone or in combination, are responsible for nearly all cases of severe ICU acquired muscle weakness.