Cardiac effects of carbon dioxide-consuming and carbon dioxide-generating buffers during cardiopulmonary resuscitation.

Recent studies have demonstrated an increase in carbon dioxide (CO2) tension (PCO2) in both mixed venous and coronary vein blood early in the course of cardiac arrest and cardiopulmonary resuscitation. Because increased PCO2 in the myocardium correlates with both ischemic injury and depression of contractile function, the effects of hypertonic solutions of either the CO2-"generating" sodium bicarbonate (NaHCO3) buffer, a mixture of sodium carbonate (Na2CO3) and sodium bicarbonate (carbicarb) acting as a CO2-"consuming" buffer, or saline placebo (NaCl) were compared during cardiopulmonary resuscitation in 25 healthy minipigs. Both buffer agents significantly increased the pH and HCO3- of arterial, mixed venous and coronary vein blood. Bicarbonate increased whereas carbicarb reduced blood PCO2 in the systemic circuit as anticipated. However, neither the PCO2 nor the lactate content of coronary vein blood was favorably altered by buffer therapy. Four of eight animals treated with bicarbonate, five of eight treated with carbicarb and six of nine placebo-treated animals were successfully resuscitated and had a comparable 24 h survival rate. Coronary perfusion pressure during precordial compression, a critical determinant of resuscitability, was transiently decreased by each of the hypertonic solutions. Accordingly, neither CO2-generating nor CO2-consuming buffers mitigated increases in coronary vein PCO2 or improved the outcome of cardiopulmonary resuscitation under these experimental conditions.

Monophosphoryl lipid A stimulated up-regulation of reactive oxygen intermediates in human monocytes in vitro.

The production of reactive oxygen and nitrogen intermediates is a common response to infectious challenge in vivo. These agents have been implicated in the modulation of cytokine responses and are produced in large amounts in response to endotoxins produced by a number of infectious agents. The antigen-presenting cell activation caused by these lipopolysacchardies (LPS) has been exploited in the use of these agents as adjuvants. In recent years, less-toxic derivatives have been sought. One such agent, monophosphoryl lipid A (MPL), has been used increasingly in vivo as an adjuvant and as a modulator of the inflammatory process. It is known that this agent modulates the inflammatory response and cytokine production. In addition, we have shown its effect on the production of reactive nitrogen intermediates. In this paper, we show that MPL stimulates the release of high levels of superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)), the latter being greater than that seen with LPS and appearing to be related to the inability of MPL to stimulate catalase activity. When cells were pretreated with LPS or MPL and subsequently challenged with LPS, the production of O(2)(-) and H(2)O(2) was inhibited significantly by LPS and MPL. The concentration of MPL required to induce significant hyporesponsiveness to subsequent LPS challenge was 10 times lower than that of LPS. Hyporesponsiveness was greatest when induced by 10 microg/ml MPL, the same concentration that induced the maximum release of H(2)O(2) in primary stimulation. In addition, we have shown that following MPL pretreatment, LPS stimulation does not cause the loss of cytoplasmic IkappaBalpha, which occurs when human monocytes are cultured with LPS. From our results, we propose a model for the reduced toxicity of MPL.

Decreases in mortality on a large urban medical service by facilitating access to critical care. An alternative to rationing.

The admission and case fatality rate (CFR) on a large urban medical service for 12 months before and after the creation of an intermediate care unit were examined. In the year after the intermediate care unit was opened, total admissions to the ICU/CCU decreased by 7.1% as a result of a 14.6% decrease in admission of low-risk patients who did not require critical care services. The CFR of patients on the medical service decreased by 13.3% in the year after implementation of the intermediate care unit. The decrease in mortality was accounted for by a 25.0% decrease in general ward deaths and a 38.8% decrease in ward cardiac arrests. There was no significant difference in the ICU/CCU CFR. The admission of low-risk patients to an intermediate care unit provided greater access to intensive care and was associated with an overall lower medical service CFR.

Septic encephalopathy. Evidence for altered phenylalanine metabolism and comparison with hepatic encephalopathy.

We elected to test the hypothesis that the metabolic encephalopathy associated with systemic sepsis may have a pathogenesis that is similar to hepatic encepathology, ie, as the consequence of hepatic dysfunction that induces alterations in synthesis of catecholic and noncatecholic neurotransmitters. Eleven patients with septic encephalopathy were compared with nine patients with septic encephalopathy and nine normal controls with respect to blood and cerebrospinal fluid (CSF) amino acid profile, phenylethylamine and its metabolite phenylacetic acid, and blood ammonia. Blood and CSF levels of phenylacetic acid increased markedly in septic and hepatic encephalopathy while CSF phenylethylamine levels were not increased in either condition, presumably due to rapid turnover. The CSF concentrations of all the aromatic amino acids were increased in hepatic encephalopathy, whereas in the patients with sepsis, only phenylalanine levels were increased. Evidence of stimulated neutral amino acid transport into brain was demonstrated in hepatic not septic encephalopathy and appeared to correlate with the CSF glutamine concentration. Blood ammonia levels were increased in hepatic but not in septic encephalopathy. Our data support the hypothesis that metabolites of phenylethylamine contribute to encephalopathy in systemic sepsis and hepatic failure; however, the entities differ in other respects.

Triage considerations in medical intensive care.

As an initial step toward improving admission criteria to the medical intensive care unit (MICU), we examined Acute Physiologic and Chronic Health Evaluation scores and the diagnosis-adjusted mortality rates of 2419 medical patients, including those who received MICU consultation over a 6-month period. There was considerable overlap in the physiologic scores and the predicted mortality rates between those patients who were admitted to the MICU and those who were not. There was no discrete score or mortality rate at which triage to the MICU would have included most MICU patients but excluded most patients who survived without admission to the MICU. While uniform MICU admission criteria would be desirable, current scoring systems may not have the desired sensitivity or specificity to establish such criteria. Using a receiver operating characteristic curve, we demonstrated that diagnosis-adjusted mortality rates could predict as well as Acute Physiologic and Chronic Health Evaluation scores which patients would receive MICU admission and intervention. This suggests that, for different diagnoses, specific clinical variables and laboratory tests may have different predictive importance for MICU admission. Prospective models of clinical variables using receiver operating characteristic curves in various medical diseases may improve triage procedures.

End tidal carbon dioxide as an haemodynamic determinant of cardiopulmonary resuscitation in the rat.

End tidal PCO2 (PETCO2) has been found to be a good prognostic indicator of successful resuscitation from cardiac arrest. To explore the value of this measurement further, we carried out a series of experiments during cardiac arrest and closed chest resuscitation in 14 mechanically ventilated Sprague-Dawley rats. Ventricular fibrillation (VF) was induced by a 10 mA current delivered to the right ventricular endocardium. After 4 min of VF, precordial compression was begun with a mechanical thumper and defibrillation was attempted 2 min later. PETCO2 decreased abruptly during cardiac arrest to 0.3 mm Hg (0.04 kPa). With precordial compression, it increased to 11 mm Hg (1.5 kPa). Within 3 min of successful defibrillation, there was an overshoot in the PETCO2 to 44 mm Hg (5.8 kPa) with return to baseline levels approximating those of the pre-arrest control measurements over the 60 min that followed restoration of spontaneous circulation. The PETCO2 measurement during precordial compression predicted the success of defibrillation with return of spontaneous circulation. When PETCO2 exceeded 9 mm Hg (1.2 kpA), 7 of 8 animals were successfully resuscitated. When PETCO2 was less than 9 mm Hg during precordial compression, none of six animals were successfully resuscitated. The PETCO2 correlated with the mean aortic (r = 0.71) and coronary perfusion pressure (r = 0.80) generated during precordial compression. In corroboration of previously reported observations on pigs, dogs, and human patients, PETCO2 served as a non-invasive monitor of the effectiveness of precordial compression for maintaining coronary perfusion and therefore cardiac viability during CPR. The PETCO2 was also useful in that it promptly signalled restoration of spontaneous circulation.

Uremic pulmonary edema.

Pulmonary edema fluid analyses and hemodynamic evaluations were performed in two uremic patients with acute pulmonary edema. The colloid osmotic pressure of the pulmonary edema fluid ranged from 57 per cent to 93 per cent that of the serum. Although cardiac function was normal in both patients, the serum colloid osmotic pressure--pulmonary artery wedge pressure gradients were markedly reduced. Uremic pulmonary edema is the result of alterations of pulmonary intravascular Starling forces and increases in pulmonary capillary membrane permeability, allowing for the efflux of protein-rich fluid from the capillaries into the lung.

Effect of crystalloid and colloid solutions on blood rheology in sepsis.

Sepsis is associated with altered blood rheology. Fluid infusion is an essential component of therapy for septic shock. The purpose of this study was to compare the rheologic changes associated with saline, albumin, and hydroxyethyl starch in sepsis. Whole blood was obtained from five normal controls and five patients with severe sepsis. The samples were centrifuged, and the erythrocytes were resuspended in autologous plasma or autologous plasma plus the buffy coat at an hematocrit (Hct) of 40%. The sample was diluted to an Hct of 30%, 20%, and 10% with saline, albumin, or hydroxyethyl starch. Viscosity was measured at low and high shear rates and erythrocyte aggregation was measured by the ratio of viscosity at low to high shear rates. Erythrocyte deformability was assessed by filtration. The viscosity of hydroxyethyl starch was greater than saline, albumin, or autologous plasma (p < .01). Erythrocyte viscosity was greater (p < .01) and deformability less (p < .01) in septic blood compared with normals. Dilution with hydroxyethyl starch increased erythrocyte viscosity as compared with saline (p < .01) and albumin (p < .01). Erythrocyte deformability was decreased with both hydroxyethyl starch (p < .001) and albumin (p < .05) compared with saline. Increased erythrocyte aggregation was also observed with hydroxyethyl starch (p < .05) and albumin (NS) in septic cells when compared with saline. These data indicate that hydroxyethyl starch increases blood viscosity, decreases erythrocyte deformability, and increases erythrocyte aggregation when compared with saline. These changes are less significant with albumin. In patients with sepsis, these effects may further compromise the already altered erythrocyte rheology.

Monophosphoryl lipid A protects against gram-positive sepsis and tumor necrosis factor.

Monophosphoryl lipid A (MPL) is a less toxic derivative of lipid A that enhances survival from endotoxemia. This study examined whether MPL induced resistance to Gram-positive sepsis and cytokines. Mice were administered MPL or saline (phosphate-buffered saline) and challenged 24 h later with live Staphylococcus aureus (SA), staphylococcus enterotoxin B (SEB), toxic shock syndrome toxin (TSST-1), and tumor necrosis factor (TNF). Survival was determined at 72 h. A separate set of animals was phlebotomized for determination of cytokines. MPL increased survival from S. aureus bacteremia from 20 to 87% (p < .05). Interleukin-6 (IL-6) and interleukin-1 (IL-1) and TNF were also significantly decreased. SEB and TSST survival were enhanced from 10 to 90% (p < .05). In SEB-treated animals, TNF and IL-6 levels were significantly decreased. Survival from TNF infusion was increased from 20 to 100% with MPL, however, no significant differences in cytokines were observed. These data suggest that MPL induces resistance to Gram-positive sepsis and cytokine-mediated activity.

Neurogenic pulmonary edema.

This report presents a patient who developed fulminant pulmonary edema as a complication of an acute subarachnoid hemorrhage. Hemodynamic evaluation revealed low-normal pulmonary arteriolar resistances. Endobronchial fluid was freely suctioned from the patient over a two-day period and had a colloid osmotic pressure and protein content equal to the patient's plasma throughout the entire course. These findings suggest that neurogenic pulmonary edema in this patient was related to increased capillary permeability and may occur independent of pulmonary hemodynamics.

Colloid osmotic pressure as a prognostic indicator of pulmonary edema and mortality in the critically ill.

The relationship of colloid osmotic pressure (COP) to pulmonary edema and mortality in 128 critically ill patients was investigated in our critical care unit, and confirms previously reported observations. The COP in the 86 survivors was 22.0 (+/- 0.4 SEM) mm Hg versus 17.2 (+/- 0.6 SEM) mm Hg in the 42 who died (P less than 0.001). The patients were divided into three groups: 71 with no pulmonary edema, COP of 21.5 (+/- 0.5 SEM) mm Hg; 40 with cardiogenic pulmonary edema, COP of 21.4 (+/- 0.4 SEM) mm Hg; and 17 with noncardiogenic pulmonary edema, COP OF 13.6 (+/- 0.8 SEM) mm Hg. Colloid osmotic pressure was significantly lower in patients with noncardiogenic pulmonary edema (P less than 0.001). In 36 patients in whom pulmonary artery wedge pressures (PWP) were available, a COP-PWP gradient of 4.0 mm Hg or less was always associated with pulmonary edema, while a COP-PWP gradient greater than 4.0 mm Hg was never associated with pulmonary edema. Colloid osmotic pressure is a useful prognostic indicator of pulmonary edema and mortality in the critically ill.

The relationship of the colloid osmotic-pulmonary artery wedge pressure gradient to pulmonary edema and mortality in critically ill patients.

The relationship of serum colloid osmotic pressure (COP) and pulmonary artery wedge pressure (PAWP) to pulmonary edema and mortality was investigated in 76 critically ill patients. Forty patients suffered from circulatory shock and 36 did not. The COP-PAWP gradient and radiographic evidence of pulmonary edema were measured at the time of diagnosis. The COP-PAWP gradient was markedly decreased in both shock and non-shock patients with pulmonary edema. Decrease of the COP-PAWP gradient correlated with mortality only in those patients with shock. The shock patients who died had a significantly higher incidence of pulmonary edema than those who survived, whereas there was no difference in the incidence of pulmonary edema for surviving or dying non-shock patients. We conclude that marked decreases of the COP-PAWP gradient predict pulmonary edema in the critically ill, but predict mortality only for patients with circulatory shock.

The relationship between oxygen delivery and consumption during fluid resuscitation of hypovolemic and septic shock.

The effects of increasing oxygen delivery (DO2) on oxygen consumption (VO2) in eight patients with septic shock and five patients with hypovolemic shock were studied during fluid resuscitation. In the septic shock group, DO2 increased from 315 +/- 29 to 424 +/- 25 ml/min/m2 (p less than 0.01) and VO2 increased from 134 +/- 8 to 151 +/- 7 ml/min/m2 (p less than 0.01). In the hypovolemic shock group, DO2 increased from 239 +/- 26 to 386 +/- 48 ml/min/m2 (p less than 0.01) and VO2 increased from 96 +/- 9 to 135 +/- 6 ml/min/m2 (p less than 0.01). There was no significant difference in either the increase in DO2 or VO2 between the septic shock and hypovolemic shock patients. We conclude that increasing DO2 by fluid resuscitation increases VO2 during both hypovolemic and septic shock.

End-tidal carbon dioxide tension as a monitor of native blood flow during resuscitation by extracorporeal circulation.

In a porcine model of cardiac arrest, we investigated end-tidal carbon dioxide tension as a monitor of native blood flow during resuscitation by extracorporeal circulation. After 15 minutes of cardiac arrest and after precordial compression and transthoracic countershocks had failed, extracorporeal circulation consistently restored spontaneous circulation. Native end-tidal carbon dioxide tension, which averaged 29.8 +/- 1.0 mm Hg before arrest, was only 5.2 +/- 0.8 mm Hg during precordial compression. After the start of extracorporeal circulation, native end-tidal carbon dioxide tension was measured during 15-second interruptions of pump flow. End-tidal carbon dioxide tension progressively increased with a corresponding increase in native cardiac index. The correlation coefficients between end-tidal carbon dioxide tension and native cardiac index averaged 0.92 +/- 0.03 (mean +/- standard error of the mean). When end-tidal carbon dioxide tension exceeded 15 mm Hg, mean aortic pressure in each instance was 60 mm Hg or greater, and the animal was successfully weaned from extracorporeal support. We conclude that end-tidal carbon dioxide tension serves as a reliable monitor of blood flow through the lung and therefore of native cardiac output during weaning from extracorporeal circulation. It therefore indicates when native cardiac output is likely to be adequate to sustain spontaneous circulation.

Massive hemoptysis during catheterization of the internal jugular vein.

Percutaneous cannulation of the internal jugular vein is commonly performed to obtain central venous access. We report the first case of massive hemoptysis occurring during cannulation of the internal jugular vein.

Improved survival in patients with AIDS, Pneumocystis carinii pneumonia, and severe respiratory failure.

Pneumocystis carinii pneumonia (PCP) causing acute respiratory failure (ARF) in patients with acquired immunodeficiency syndrome (AIDS) has been reported in several studies to have a mortality of 84 to 100 percent. A recent report found a 42 percent survival rate. We followed 58 patients with AIDS who required positive pressure ventilation and identified 33 patients with PCP and ARF who had a PaO2/FIo2 level less than 150 mmHg. We report the survival of 12 of these 33 (36 percent). The mean duration of survival after discharge from the hospital was 7.9 +/- 1.8 months, which is an improvement over previous reports. These data suggest that we should reevaluate the reported recommendations that patients with AIDS, PCP and ARF should not receive intensive care or mechanical ventilation.

Pulmonary edema; a complication of diabetic ketoacidosis.

Hemodynamic evaluation in two patients and analysis of pulmonary edema fluid in one patient with diabetic ketoacidosis and acute pulmonary edema were performed. Pulmonary arterial wedge pressures in both patients were low or normal (1 and 9 mm Hg). In one patient the colloid osmotic pressure of the pulmonary edema fluid was 68 percent of the value of the serum. The serum colloid osmotic pressure-pulmonary arterial wedge pressure gradient in the second patient was markedly reduced. Pulmonary edema complicating diabetic ketoacidosis may be the result of increased permeability of pulmonary capillary membranes and altered intravascular colloid-hydrostatic forces.

Altered leukocyte immunophenotypes in septic shock. Studies of HLA-DR, CD11b, CD14, and IL-2R expression.

To evaluate the role of cellular activation markers and functional surface molecules in sepsis, specific immunophenotypes on peripheral blood leukocytes were studied in 40 subjects consisting of the following: (1) patients with septic shock; (2) patients with sepsis; (3) critically ill nonseptic patients; and (4) normal control subjects. These assays included phagocyte adhesion molecule CD11b expression, monocyte receptors HLA-DR and CD14, and lymphocyte activation markers IL-2R and HLA-DR. Patients with septic shock and sepsis had significantly increased neutrophil CD11b expression compared with normal subjects. Neutrophil HLA-DR expression did not significantly differ between groups. Monocytes from septic shock patients had significantly less HLA-DR expression than normal subjects and there was a trend toward a lower proportion of gated monocytes that expressed CD14 in septic shock patients. Septic shock patients had no significant increases in IL-2R or HLA-DR expression on CD3 lymphocytes compared with control subjects, but they had significantly lower numbers of total, CD3, CD4, and CD8 lymphocytes and a higher prevalence of anergy. Septic shock patients manifested an increase in neutrophil CD11b expression that may play a role in organ injury. In contrast, a more specific decrease in monocyte expression of functional antigens is also observed in patients with septic shock that may have implications for immunologic defense mechanisms.

Skeletal muscle blood flow and venous capacitance in patients with severe sepsis and systemic hypoperfusion.

Alterations in peripheral vascular tone are presumed to contribute to circulatory failure during severe sepsis. Decreased venous tone with venous pooling may decrease effective circulatory blood volume, while decreased arterial tone with redistribution of systemic blood may compromise tissue nutrient flow. We compared forearm arterial and venous tone and forearm blood flow in ten patients with and ten patients without sepsis. The FVT, MVC, and FBF were measured by air plethysmography. In the septic patients, MCV was 1.4 +/- 0.1 ml compared with 3.1 +/- 0.2 ml in nonseptic patients (p less than 0.01). The FVT was 13.4 +/- 1.0 mm Hg/ml in septic patients versus 7.0 +/- 0.5 mm Hg/ml in nonseptic patients (p less than 0.01). The ratio of FBF to cardiac output was 0.28 +/- 0.07 percent in septic patients and 0.31 +/- 0.07 percent in nonseptic patients. These data suggest that increased peripheral venous capacitance and redistribution of skeletal muscle blood flow are not present in patients with sepsis.

Non-ICU care of hemodynamically stable mechanically ventilated patients.

OBJECTIVE: To analyze a 4 1/2-year experience caring for hemodynamically stable mechanically ventilated patients on a nonmonitored respiratory care floor (RCF) for therapeutic outcome, utilization, and costs. DESIGN: A retrospective medical records review. SETTING: ICUs and an RCF of a university-affiliated tertiary care center. PARTICIPANTS: Two hundred twenty-four patients requiring more than 24 h of mechanical ventilation cared for on the RCF. RESULTS: The mean age of patients was 67 +/- 17 years. Of the admissions, 58% were from the medical ICU, 28% were from surgical ICUs, and 9.4% were from general medical floors. Patients spent 50 +/- 66 days mechanically ventilated on the RCF. Overall survival was 50.4% with 93.8% of surviving patients successfully weaned from mechanical ventilation. Survival by diagnostic group demonstrated highest probability of survival in patients with trauma and lowest in patients with multisystem failure. Of the survivors, 39% were discharged home, 34% to a rehabilitation unit, and 24% to a skilled nursing facility. Savings based on differential of costs between the ICU and RCF, primarily from reduced staffing requirements, were estimated at $4.1 million. CONCLUSION: Use of a nonmonitored RCF for the care of hemodynamically stable mechanically ventilated patients yields acceptable therapeutic outcomes while providing the institution with increased flexibility in critical care bed management and significant financial savings.