Randolph P. Cole

Skeletal muscle function in hypoxia: Effect of alteration of intracellular myoglobin

Enhancement of oxygen flux through myoglobin containing solutions due to myoglobin facilitated oxygen diffusion is well recognized and is most apparent under conditions of hypoxia. To examine the function of intracellular myoglobin in vivo under conditions of hypoxia, the in situ dog gastrocnemius-plantaris muscle was studied. Administration of 10% oxygen resulted in arterial PO2 values between 32 and 36 mm Hg. Muscle oxygen consumption and isometric tension generation were determined during sustained 3-Hz contractions before and after administration of hydrogen peroxide that converted functional myoglobin to forms incapable of reversible combination with oxygen. Muscle blood flow, perfusion pressure, and muscle oxygen delivery were unchanged by such treatment. Hydrogen peroxide administration resulted in oxidation of intracellular myoglobin with a resultant decrease of 37% in muscle oxygen consumption and 42% in tension generation after 20 min of stimulation. In a control group not receiving hydrogen peroxide muscle oxygen consumption and tension generation decreased by 13% and 12%, respectively. We conclude that intact functional myoglobin is important in maintaining muscle function in isometric exercise under conditions of hypoxia.

Myopathy in Status Asthmaticus: Relation to Neuromuscular Blockade and Corticosteroid Administration

Myopathy is a rare complication that arises during management of status asthmaticus that may be related to administration of corticosteroids and neuromuscular blocking agents. We present 4 patients with myopathy and a review of the 31 previously reported patients in the literature. All patients received corticosteroids, and 33 of the 35 patients received neuromuscular blocking agents. Muscle weakness was often diffuse and, in several patients, involved the muscles of respiration. Creatine kinase values ranged from normal to markedly elevated. Diagnosis was obtained by electromyogram and muscle biopsy in most patients. Resolution of the muscle weakness occurred over a period of days to months. Patients in whom myopathy developed required mechanical ventilation for longer periods than patients intubated for status asthmaticus without myopathy.

Evolving differences in the presentation of severe asthma requiring intensive care unit admission.

Background: The prevalence of asthma in the community has been increasing. Asthma mortality has not followed the same pattern. Patients who present with a severe asthma exacerbation share many characteristics with patients who die from asthma. Objective: We examined the differences in the presentation of severe asthma in adults admitted to a medical intensive care unit (MICU) over a 10-year interval. Methods: We reviewed the records of the MICU at the Columbia Presbyterian Medical Center for all admissions with severe asthma for the period from January 2000 to December 2001. The data collected included the number of admissions per month, baseline characteristics, initial arterial pH and PCO2, length of ICU stay, and complications. These data were compared with similar data obtained over the period 1990–1991. Results: The number of MICU admissions per month for severe asthma decreased from 3.1 in 1990–1991 to 0.8 in 2000–2001. There was a trend toward a reduction in asthma severity as determined by a decrease in the initial arterial PCO2 from 80 ± 27 to 55 ± 23 mm Hg and an increase in pH from 7.1 ± 0.14 to 7.23 ± 0.14 (0.10 > p > 0.05 for both). There was 1 death from severe hypoxemia and respiratory acidosis in the earlier series and no asthma deaths in the later series. Conclusion: In our institution, there has been a decline in the number of patients with status asthmaticus requiring ICU admission over the past 10 years and a trend towards less advanced presentations with reduced levels of respiratory acidosis and decreased ICU length of stay. These changes may be related to improved medications, education, or access to care in the community.

Bullous emphysema occurring in pulmonary sarcoidosis.

We describe a rare case of bullous emphysema occurring in a young male with sarcoidosis. The patient had progressive pulmonary symptoms over 14 years. Chest radiology showed bilateral bullae predominantly of both upper and the left lower lobes and mild bronchiectasis. Pulmonary function tests revealed mild restrictive disease and a severe reduction in diffusion capacity. Loss of alveolar surface area due to bullous disease contributes to functional and physiological impairment of lung function in sarcoidosis.

Prognostic Indicators in Patients with the Acquired Immune Deficiency Syndrome (AIDS) and Respiratory Infection

The records of 63 patients with acquired immune deficiency syndrome (AIDS) and respiratory infection comprising 78 hospitalizations over a 36-month period were reviewed to ascertain the etiology of the respiratory infection and to identify the factors influencing short-term survival. Pneumocystis carinii pneumonia (PCP) was diagnosed on 56 occasions in 46 patients. Fifty percent of patients with PCP died with respiratory failure; of these, all but 1 were diagnosed using fiber-optic bronchoscopy. In 18 patients in whom PCP was not identified by bronchoscopy, the in-hospital mortality was 17%. Of the clinical and laboratory findings on admission, only the arterial PO2 and the alveolar-arterial PO2 (AaPO2) difference were significantly different between the survivors and nonsurvivors. In patients with PCP and a AaPO2 greater than 60 mm Hg, 92% died. The demonstration of P. carinii by fiber-optic bronchoscopy and the presence of markedly abnormal gas exchange are associated with high in-hospital mortality.

Effect of Bronchoalveolar Lavage on Gas Exchange in Patients with Diffuse Lung Disease and Respiratory Failure

The effect of fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) on arterial oxygenation was examined in 22 patients with acute respiratory failure requiring mechanical ventilatory support. Arterial blood gases were determined immediately prior to BAL and at 15, 60, 120, and 360 minutes following BAL. PaO2/FIO2 decreased at 15 minutes and continued to decrease to approximately 33% below the baseline value at 2 hours. PaO2/FIO2 then remained constant over the remainder of the 6-hour study period. No substantial changes in FIO2, level of positive end-expiratory pressure, or intravenous pressor requirements occurred during the period of observation. Patients with lower pre-BAL PaO2/FIO2 ratios showed the least reduction in PaO2/FiO2 following BAL The BAL was diagnostic in 9 of 22 (41%) patients (Pneumocystis carinii pneumonia in 5, bacterial pneumonitis in 2, and neoplastic involvement of the lung in 2). BAL was associated with mild deterioration of gas exchange but did not require significant changes in ventilatory or hemodynamic support for the 6-hour interval studied.

Factitious Intrinsic PEEP in a Patient with Respiratory Failure

There have been reports on certain new model ventilators, including the Mallinckrodt Series 840 ventilators (St. Louis, Mo., USA). Their expiratory tidal volumes are said to be larger than preset inspiratory tidal volumes when the oxygen supply to the inflation circuit nebulizer is not turned off. We report a situation where the unrecognized continuous nebulizer gas flow was interpreted as substantial intrinsic positive end-expiratory pressure (PEEP) in a patient with chronic obstructive lung disease and respiratory failure. The patient, a 53-year-old male, was admitted with weight loss, fever and dyspnea, and his chest radiograph showed a right hilar mass and complete atelectasis of the right lung without mediastinal shift. At bronchoscopy, a mass occluding the right main stem bronchus was noted, and biopsy revealed squamous-cell carcinoma. In hospital, he received broad-spectrum antibiotics and local external beam radiotherapy, and after nine of the ten planned courses of radiation had improved breath sounds in the right hemithorax. He was later found unresponsive with pulseless electrical activity on the ECG. He responded to resuscitative measures; in the intensive care unit, his systemic blood pressure was 100/65 mm Hg while he received intravenous norepinephrine 10 Ìg/min. On examination, diffuse wheezing with muffled heart sounds and no jugular venous distension were noticed, and he had warm distal extremities. On assist-control volume ventilation mode, tidal volume was 550 ml, external PEEP 5 cm H2O and respiratory rate 12/min, peak airway pressure 35 cm H2O. With an end-expiratory pause of 1 s, intrinsic PEEP was 12 cm H2O and total PEEP was 17 cm H2O. Addition of 12 cm H2O external PEEP caused the inflation pressure to increase to 42 cm H2O and had no effect on the total PEEP. It was then appreciated that the oxygen flow to the in-line nebulizer was 10 l/min. After reducing the gas flow to zero, a repeated measurement of intrinsic PEEP by end-expiratory pause with external PEEP of 5 cm H2O showed 1.6 cm H2O. In the patient with airway obstruction receiving mechanical ventilatory support, the presence of a nonzero flow at end expiration may lead to the development of intrinsic PEEP [1]. If flow limitation is present, the application of external PEEP may improve expiratory flow without producing excessive hyperinflation or increasing inflation pressure. On the other hand, active expiratory efforts can generate expiratory flow both in the presence and absence of airflow obstruction [2]. In our patient, sedation and the absence of abdominal wall muscular tone during the respiratory cycle suggested that there was no active expiration. The presence of subcutaneous emphysema under greater than atmospheric pressure with expiratory emptying into the airways has been termed ‘pseudo auto-PEEP’ [3] and can be confused with prolonged expiratory flow from airway disease. In the current situation, an unrecognized nebulizer gas flow in a patient with clear airflow obstruction and prolonged expiratory wheezing led to the incorrect conclusion that significant intrinsic PEEP was present and to an attempt to improve expiratory airflow and reduce inspiratory work of breathing by the addition of external PEEP. The higher than expected increase in inflation pressure noted after PEEP addition led to the recognition of the additional ventilator nebulizer flow. The nebulizer gas flow should be discontinued between aerosol nebulizer treatments before the determination of respiratory system mechanics, to allow an accurate determination of intrinsic PEEP in patients with airflow obstruction.