Frederick L. Glauser

Relationship between cardiac output and the end-trial carbon dioxide tension

STUDY OBJECTIVE To further define the relationship between cardiac output (CO) and end-tidal carbon dioxide tension (ETCO2) at various levels of systemic flow. DESIGN Prospective, controlled laboratory investigation. SETTING Animal laboratory. TYPE OF PARTICIPANTS Fourteen anesthetized, intubated sheep weighing 23 to 47 kg. INTERVENTIONS One hundred seventy-two simultaneous measurements of thermodilution CO and ETCO2 were made during controlled arterial hemorrhage. After a 30-minute baseline control period, CO was sampled from approximately 0.6 to more than 8.0 L/min during a 60- to 90-minute period of controlled hemorrhage. MEASUREMENTS Thermodilution CO; arterial pressure using fluid-filled plastic 14-gauge catheters; ETCO2 using an infrared analyzer. MAIN RESULTS A plot of CO versus ETCO2 suggested that the relationship was logarithmic rather than linear. Linear regression showed that ETCO2 was significantly related (r = .91; P less than .001) to a logarithmic transformation of the CO. CONCLUSIONS The relationship between CO and ETCO2 is logarithmic. Decreased presentation of CO2 to the lungs is the major, rate-limiting determinant of the ETCO2 during low flow. As the CO increases during resuscitation from shock or cardiac arrest, respiration becomes the rate-limiting controller of the ETCO2 (after the tissue washout of CO2 has occurred). Under such conditions, the ETCO2 provides useful information about the adequacy of ventilation provided that there is little ventilation/perfusion mismatch.

Central venous catheter infections: concepts and controversies

Central venous catheters (CVCs) are widely used in critically ill patients in intensive care units. However, infectious complications are common and may limit their utility. We critically review the literature to determine the impact of CVC design amd composition, insertion site selection, insertion procedures, care and removal of temporary CVCs on infectious complications. Relevant articles were identified and selected for review using a database search (Medline and manual of the English language literature) based upon study design and sample size with an emphasis on prospective randomized trials. To minimize infectious complications and maintain a reasonable cost-benefit ratio, we recommend: i) use a single lumen catheter unless clear indications for a multi-lumen catheter exist; ii) insert the catheter via the subclavian vein if no relative contraindication exists (bleeding diathesis, positive pressure ventilation); iii) disinfect the insertion site employing sterile technique; iv) apply a dry, sterile dressing and change the dressing every other day; v) inspect the insertion site for signs of infection and remove the catheter if pus is present; vi) if a catheter-related infection is suspected, change the catheter over a guidewire and culture the distal segment. The replacement catheter should be removed if an original catheter segment culture is positive.

Prolonged isoflurane anesthesia in status asthmaticus.

We report a case of status asthmaticus that was unresponsive to the usual agents. The use of an inhalational anesthetic agent allowed us to ventilate the patient with lower inspiratory pressures; however, lasting improvement did not occur until she mobilized large quantities of secretions. To our knowledge, this is the first clinical report on the use of isoflurane anesthesia to treat severe asthma. Despite prolonged administration, there were no significant side-effects. This case demonstrates both the benefits and limitations of such therapy.

Cardiac Arrhythmias and ECG Abnormalities in Tricyclic Antidepressant Overdose

Tricyclic antidepressant overdose is widely felt to be associated with cardiac arrhythmias which may occur without warning, sometimes late in the clinical course. For this reason, many institutions routinely monitor cardiac rhythm in such patients for up to 72 h. A retrospective study was carried out to analyze the clinical course of such patients with emphasis on cardiac complications. Thirty-eight cases of TCA overdose were reviewed. Fourteen patients (36.9%) were classified as lethargic or stuporous on admission while 23 (60.5%) were either comatose or semicomatose, nine requiring endotracheal intubation. Patients were continuously monitored an average of 60 h after admission. Admission ECGs were abnormal in a high number of cases, most common abnormalities being sinus tachycardia (43%) and intraventricular conduction defects (24%). Ventricular ectopy was less common (7.8%). ECG abnormalities, with the exception of sinus tachycardia and infrequent PVCs were associated with a severely depressed sensorium and disappeared with neurological improvement, usually in 24 h. No arrhythmias were noted after the patient had become alert. Overall mortality was 2.6%, with no deaths in the adult populations. After a search of the literature, we conclude that intensive care unit monitoring is not indicated for prolonged periods once the patient has otherwise recovered from his acute complications of drug overdose.

Effects of isosorbide dinitrate on pulmonary hypertension in chronic obstructive pulmonary disease.

Eighteen patients with chronic obstructive pulmonary disease with pulmonary hypertension were studied to assess the hemodynamic response to acute oxygen administration and to oral isosorbide dinitrate (ISDN). All 18 patients had baseline hemodynamic measurements and hemodynamic measurements during low‐flow nasal oxygen. Following a second baseline measurement, patients received either oral ISDN (11 patients) or placebo (7 patients) in a randomized, double‐blind protocol. Heart rate decreased with oxygen administration but there were no other significant hemodynamic changes. With oral ISDN, there was a significant fall in pulmonary artery and brachial artery pressure. Cardiac output, right atrial pressure, pulmonary wedge pressure, and pulmonary vascular resistance all fell but not significantly. We conclude that oral ISDN is effective in reducing pulmonary hypertension in patients with chronic obstructive pulmonary disease.

Hypercarbic arterial acidemia following resuscitation from severe hemorrhagic shock

Arteriovenous pH and PCO2 gradients can develop during low cardiac output states. We have seen a transient rise in arterial PCO2 and a fall in arterial pH in humans receiving closed-chest cardiopulmonary resuscitation immediately following restoration of spontaneous circulation. Using a hemorrhagic shock model in sheep, serial arterial and mixed venous blood gases were sampled and CO2 elimination was measured. When cardiac output was less than 30% of the baseline value and the arteriovenous PCO2 difference was greater than 20 mmHg, the animals were rapidly resuscitated with intravenous 0.9% NaCl and dopamine. Following resuscitation, there was a transient arterial acidosis and hypercarbia due to passage of venous blood with a high CO2 content into arterial blood. The clinical implications in the setting of hemorrhagic shock are that (1) arterial blood gases are poor indicators of the systemic acid-base state, (2) arterial blood gases drawn immediately following volume resuscitation may be misinterpreted and should probably not be used to guide therapy and (3) there is a transient hypercarbic arterial acidosis following volume resuscitation that may have deleterious effects on cardiac and cerebral function in the early post-resuscitative period.

P pulmonale in status asthmaticus

We studied 129 patients during acute, severe asthmatic attacks. Electrocardiograms showed P pulmonale in 49% of patients who had an arterial carbon dioxide tension (PaCo2) greater than or equal to 45 mm Hg and an arterial pH less than or equal to 7.37, whereas P pulmonale was present in only 2.5% of asthmatics who had a PaCO2 less than or equal to 44 mm Hg and a pH greater than or equal to 7.38 (p less than 0.001). P wave and QRS axes were 79 +/- 8 degrees and 80 +/- 20 degrees, respectively, in the presence of P pulmonale. When P pulmonale disappeared, the P wave and QRS axes shifted significantly to the left (p less than 0.001). Electrocardiographic P pulmonale persisted 12 to 60 hr after correction of hypoxemia, hypercapnia, and acidosis. In 7 patients with P pulmonale and respiratory acidosis, cardiac catheterization demonstrated normal artery pressures (PAPs) measured relative to atmospheric pressure. In 12 of these peak inspiratory pulmonary artery transmural pressures (PATPs) were increased. Since increased right heart transumural pressures could result in chamber distention, these data are consistent with the hypothesis that reversible P pulmonale in status asthmaticus is explainable on the basis of markedly negative tidal pleural pressures and increased right heart transmural pressures.

Significance of the pulmonary artery diastolic-pulmonary wedge pressure gradient in sepsis.

An initially widened pulmonary artery diastole-pulmonary wedge pressure (PAD-PWP) gradient >5 mm Hg has been reported to be associated with an 83% mortality rate in septic patients. To confirm and extend these observations, we retrospectively reviewed the charts of 47 septic patients. The patients were divided into 2 groups: group 1—12 patients who never had an abnormal gradient during their hospital course, and group 2–35 patients who had an abnormal gradient sometimes during their course. There were no hemodynamic differences. However, the mortality rate in group 2 patients was significantly higher than in group 1 patients (60% vs 25%, p <0.01). In patients with an initial gradient, the mortality rate was 61% which is not significantly different than the 83% previously reported. In patients with a persistent or increasing gradient before death or the resolution of sepsis, the mortality rate was 91%. We conclude that although an initial PAD-PWP gradient in patients with sepsis is associated with a high mortality, a much more sensitive indicator is whether the gradient increases or persists over time. There is a 91% mortality in patients with persisting or increasing gradients.

Nonspecific Cytotoxicity of Recombinant Interleukin-2 Activated Lymphocytes

The administration of interleukin-2 (IL-2) and lymphokine activated killer (LAK) cells to patients with advanced metastatic cancer has yielded encouraging results. The purported ability of LAK cells to be discriminatively tumoricidal, thus sparing normal host tissue, represents a major advance over conventional chemotherapy. However, IL-2 adoptive immunotherapy results in dose-limiting toxicity characterized by weight gain, dyspnea, ascites, and peripheral-pulmonary edema suggestive of a vascular leak syndrome. It is unclear whether the observed toxicity is directly related to IL-2 and/or LAK cells. The authors examined the cytolytic nature of human LAK cells against human endothelial, epithelial, and fibroblast cell lines. Bovine endothelial cells also were studied. Using a 51Cr release assay, the cytolytic potential, time course, and effect of reactive oxygen intermediate inhibitors were studied. LAK cells were uniformly toxic against all cell lines, in contrast to high dose rIL-2 and excipient. Significant cytolysis was observed within 30 minutes and increased over the first 2 hours of LAK cells coming in contact with target cells. Reactive oxygen intermediate inhibitors did not reduce cytolytic activity. The authors thus found human LAK cells to be rapidly cytolytic against a variety of human and bovine cell lines. This cytolysis was independent of reactive oxygen intermediates.

Intravenous nitroglycerin-induced intracranial hypertension.

Nitroglycerin therapy can cause dose-related increases in intracranial pressure. Rare cases of neurologic sequelae attributed to nitroglycerin have appeared in the literature. We report such a case, in which symptoms completely resolved after cessation of nitroglycerin therapy. Widespread use of high-dose iv nitroglycerin makes knowledge of this effect important for all practitioners.