Showing papers in "Critical Care Medicine in 1993"

Mechanisms of ventilator-induced lung injury

Abstract: ObjectivesTo describe the physiologic mechanisms of ventilator-induced lung injury and to define the major ventilator and host-dependent risk factors that contribute to such injury.Data SourcesBasic science and clinical studies related to ventilator-induced barotrauma and lung pathophysiology.Study

Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study

Abstract: ObjectivePreviously, we documented that mild hypothermia (34°C) induced immediately with reperfusion after ventricular fibrillation cardiac arrest in dogs improves functional and morphologic cerebral outcome. This study was designed to test the hypothesis that a 15-min delay in the initiation of coo

Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis

Abstract: OBJECTIVES To determine the safety, pharmacokinetics, and activity of an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody in severe sepsis. DESIGN Open-label, prospective, phase II multicenter trial with escalating doses of a murine monoclonal antibody (CB0006). SETTING Twelve academic medical center intensive care units in the United States and Europe. PATIENTS Eighty patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy in addition to the anti-TNF antibody. INTERVENTIONS Patients were treated intravenously with one of four dosing regimens with CB0006: 0.1 mg/kg, 1.0 mg/kg, 10 mg/kg or two doses of 1 mg/kg 24 hrs apart. MEASUREMENTS AND MAIN RESULTS The murine monoclonal anti-TNF antibody was well tolerated despite the development of anti-murine antibodies in 98% of patients. No survival benefit was found for the total study population, but patients with increased circulating TNF concentrations at study entry appeared to benefit by the high dose anti-TNF antibody treatment. Increased interleukin (IL)-6 levels predicted a fatal outcome (p = .003), but TNF levels were not found to be a prognostic indicator. TNF levels were higher (206.7 +/- 60.7 vs. 85.9 +/- 26.1 pg/mL; p < .001) and outcome was poor (41% vs. 71% survival; p = .007) in patients who were in shock at study entry when compared with septic patients not in shock. CONCLUSIONS The murine anti-TNF-alpha monoclonal antibody CB0006 has proven to be safe in this clinical trial and may prove to be useful in septic patients with increased circulating TNF concentrations. Further studies are needed to determine efficacy and the ultimate clinical utility of this immunotherapeutic agent in sepsis.

Role of tumor necrosis factor-alpha in disease states and inflammation.

Abstract: Objective: To review the animal and human data defining the role of tumor necrosis factor (TNF) in the pathogenesis of the septic shock syndrome, the systemic inflammatory response syndrome, and related pathologic states. Data Sources: The international English language literature from 1975 to present formed the basis for this review. MEDLINE was used to identify pertinent animal and human studies. Study Selection: Those animal and human studies that focused on the mechanisms of action of TNF, its role in the inflammatory cytokine network, and the potential uses of anti-TNF therapies were emphasized. Data Extraction: Animal studies were selected based on the relevance of the model to the pathogenesis of the human systemic inflammatory response syndrome. Where they provided supportive evidence, human studies were selected on the basis of study design. Data Synthesis: TNF plays a major role in systemic inflammatory response syndrome secondary to infection, burns, trauma or hemorrhagic shock, and pancreatitis. TNF influences the outcome of other infectious processes, including allograft rejection, ischemia-reperfusion injury, delayed-type hypersensitivity, and granuloma development. The administration of anti-TNF antibodies, soluble TNF receptors, and related fusion proteins may limit organ damage and decrease mortality rate. Conclusions: Although the regulated release of TNF may exert normal physiologic effects, the uncontrolled production of TNF may lead to organ dysfunction and death. TNF mediates a variety of other physiologic processes that are unrelated to sepsis syndrome. New anti-TNF therapies appear to attenuate the injurious actions of TNF. (Crit Care Med 1993; 21:S447-S463)

Continuous veno-venous hemofiltration with dialysis removes cytokines from the circulation of septic patients.

Abstract: ObjectivesTo determine whether continuous veno-venous hemofiltration with dialysis leads to extraction of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) from the circulation of critically ill patients with sepsis and acute renal failure and to quantitate the clearance and removal rates o

Relationship between postoperative anemia and cardiac morbidity in high-risk vascular patients in the intensive care unit

Abstract: Objective.To determine if postoperative anemia is associated with postoperative myocardial ischemia and morbid cardiac eventsDesign.Case control study.Setting.Postanesthesia care unit and surgical intensive care unit.Patients.A total of 27 high-risk patients undergoing infra-inguinal arterial bypass

Regional blood flow and oxygen transport in septic shock

Abstract: ObjectiveTo measure the blood flow distribution and regional oxygen transport in hyperdynamic septic shock during hypotension and after correction by vasopressor doses of dopamine or norepinephrine.DesignProspective, randomized, controlled trial.SettingTertiary care center.PatientsTen patients with

Improved cardiovascular stability during continuous modes of renal replacement therapy in critically ill patients with acute hepatic and renal failure

Abstract: ObjectiveTo determine whether continuous modes of renal replacement therapy result in improved cardiovascular stability compared with standard daily intermittent treatment in critically ill patients.DesignProspective, randomized controlled trial.SettingIntensive care unit in a quaternary referral ce

Tumor necrosis factor : an updated review of its biology

Abstract: OBJECTIVE To review the role of tumor necrosis factor (TNF) in the pathogenesis of the septic shock syndrome. DATA SOURCES The international English language literature from 1985 to present formed the basis for this review. MEDLINE was used to identify pertinent animal and human studies pertaining to the clinically relevant aspects of TNF and related cytokines. STUDY SELECTION Those studies that focused on developments that may lead to advances in the therapy for septic shock syndrome were emphasized. Investigations that described in vivo and human results served as the primary database. DATA EXTRACTION Animal studies were selected based on the similarity of the model pathogenesis and outcomes to the human clinical sepsis syndrome. Patient studies were selected on the basis of study design and sample size. DATA SYNTHESIS The normal role of TNF and pathologic effects consequent to the excessive production of TNF in response to an overwhelming infection or injury are reviewed. Evidence establishes the role of TNF in septic shock syndrome. Novel therapies, such as anti-TNF monoclonal antibodies, soluble TNF receptors, or soluble TNF receptor-immunoglobulin G heavy chain fusion proteins, may confer protection against septic shock syndrome. CONCLUSIONS TNF plays a major role in the pathogenesis of the septic shock syndrome. TNF exerts a range of beneficial and injurious effects that may ultimately lead to organ dysfunction and death. The burst of TNF release after endotoxemia promotes the progression of the shock syndrome even in the absence of further TNF release. New therapies targeted to the attenuation of TNF may hold promise for the management of patients with septic shock syndrome.

Unreliability of blood pressure and heart rate to evaluate cardiac output in emergency resuscitation and critical illness.

Abstract: ObjectiveTo evaluate the reliability of the vital signs to evaluate circulatory stability as reflected by cardiac index.DesignDescriptive analysis based on data gathered prospectively, using a predetermined protocol.SettingUniversity-run county hospital, with a large trauma service.PatientsSixty-one

Tumor necrosis factor in the pathogenesis of infectious diseases.

Abstract: Objectives To review the immunologic role of the cytokines and the specific role that tumor necrosis factor (TNF) plays in response to infection. The influence of bacterial lipopolysaccharide on TNF, the cytokine cascade, and resultant pathologies are also reviewed. Data sources A MEDLINE search of the international English language literature from 1960 to the present was reviewed, but data from the past 5 yrs primarily formed the basis for this review. Study selection Those studies detailing the interaction of lipopolysaccharide, TNF, and other cytokines, and their roles in combating infection were emphasized. Investigations that described animal and human results served as the primary database. Data extraction Animal studies were selected based on the relevance of the model to the pathogenesis of the human clinical syndrome. Where they provided supportive evidence, patient studies were selected on the basis of study design. Data synthesis TNF plays a key role in the normal immune response to infection, limiting the spread of pathogens. Exaggerated physiologic responses occur under the influence of high concentrations of TNF that are released in response to overwhelming infection, resulting in aberrations in coagulation, cell adhesion, chemotaxis/transmigration, and vascular integrity. These pathologic effects may be inhibited by anti-TNF monoclonal antibodies and recombinant soluble receptor inhibitory proteins. Conclusions TNF exerts both physiologic and pathologic effects in response to infection; these events may lead to organ dysfunction and death. Anti-TNF therapies appear to attenuate the injurious effects of TNF.

Descriptive analysis of critical care units in the United States: patient characteristics and intensive care unit utilization.

Abstract: Objective To gather data about occupancy, admission characteristics, patients' ages, and types of therapy utilized in ICUs in the United States. Design and setting Survey instruments were mailed to the administrators of 4,233 hospitals to gather information from the medical director of the institutions' respective ICUs for the purpose of developing a database on ICUs in the United States. The sampling frame for this study was based on all American Hospital Association (AHA) hospitals stating they had ICUs. Measurements Census questionnaires solicited information on occupancy, where the patients were admitted from, length of stay, therapies rendered, intensive care diagnoses, and resuscitation status, as well as other information. Main results Data were obtained regarding 32,850 ICU beds, with 25,871 patients from 2,876 separate ICUs in 1,706 hospitals in the United States. The census response rate was 40% of the AHA hospitals that stated they had ICUs, with specific ICU data on 38.7% of the nation's ICUs. Overall, the responding units reported a mean occupancy rate of 84% of total bed capacity and 87% of available beds. As hospital size increased, so did ICU occupancy. Nearly 17% of all of the critical care patients had been in the units for > 14 days. More precisely, 49% of all responding units indicated that they had one or more "chronic" (> 14-day length of stay) patients. Most patients were admitted to the units from the emergency room (38%), operating room/postanesthesia care unit (22%), and the general hospital floor (16%). Neonatal units were exceptions to this observation, where most patients came from the delivery room (60%). Admission from other hospitals represented a significantly larger group of patients in the cardiac care, pediatric, and neonatal units. Respondents indicated that many of their current patients were elderly, with 43% of these patients aged 65 to 84 yrs and with 4% being > or = 85 yrs of age. The 47% of patients > or = 65 yrs of age increased to 58% when the neonatal and pediatric units were eliminated from the analyses. For all units responding to the survey, the leading primary admitting intensive care diagnoses were postoperative management, ischemic heart disorder, respiratory insufficiency/failure, and prematurity. Elimination of units predominantly treating children (pediatric and neonatal) from the analysis left "adult" units with three primary admitting diagnoses: ischemic heart disease, postoperative management, and respiratory insufficiency/failure with variation according to specific unit type. The leading diagnoses in pediatric units were respiratory insufficiency/failure, postoperative management, and congenital abnormalities. For neonatal units, prematurity was the primary admitting diagnosis, accounting for 59% of these units' patients. Respondents reported 5.3 +/- 10.9% of patients had received cardiopulmonary resuscitation (CPR) before admission into the critical care unit. Only 6.0 +/- 11.9% of patients in these critical care units had instructions that CPR not be performed while in the unit. Conclusions This report should be viewed as the beginning step of an effort to improve both the information base available on critical care medicine and the performance of ICUs. Our survey findings provide an introduction into the everyday workings of critical care units throughout the United States. Research is required to determine which patients will benefit from intensive care and how to efficiently utilize the vast technology we have available for them in a world with limited financial resources, an aging population, and a multiplicity of societal and ethical concerns.

Iatrogenic complications in adult intensive care units: a prospective two-center study.

Abstract: Objectivesa) To evaluate the frequency, types, severity, and morbidity of iatrogenic complications; b) determine associated factors that favor iatrogenic complications; and c) suggest new or more efficient protective measures that may be taken to improve patient safety.DesignProspective, observation

Reperfusion injury after intestinal ischemia.

Abstract: ObjectiveReview the histologic and pathophysiologic alterations seen after intestinal ischemia and reperfusion.Data SourceCurrent literature review.Study SelectionThe most pertinent, current, and representative articles describing results from both animal and human investigations are utilized and di

Association of hypomagnesemia and mortality in acutely ill medical patients.

Abstract: OBJECTIVE To test the hypothesis that the mortality rate of acutely ill patients admitted to a medical ward or medical ICU is higher for those patients who present with hypomagnesemia than for those patients who do not present with hypomagnesemia. DESIGN Prospective, observational study. SETTING Emergency Department admissions to the medical ward and medical ICU of a tertiary care teaching hospital serving an inner city patient population. SUBJECTS A total of 381 consecutive acutely ill patients. MEASUREMENTS Serum magnesium concentrations and other metabolic variables were measured on admission from the Emergency Department. Acute Physiology and Chronic Health Evaluation (APACHE II) scores were computed for all patients, and mortality rates were determined for hypomagnesemic and normomagnesemic groups. MAIN RESULTS Hypomagnesemic and normomagnesemic groups had comparable APACHE II scores and other variables. However, the mortality rates of the hypomagnesemic ward and medical ICU groups were approximately twice (p < .01) the rate of the normomagnesemic groups. Additionally, the duration of hospital survival in those patients who died was approximately 8 days less for hypomagnesemia than normomagnesemia, but not for ward admissions. Other associated metabolic abnormalities were frequently observed in both hypomagnesemic and normomagnesemic groups, including hypokalemia and hypocalcemia. CONCLUSIONS Hypomagnesemia detected at the time of admission of acutely ill medical patients is associated with an increased mortality rate for both ward and medical ICU patients.

Effects of accidental trauma on cytokine and endotoxin production.

Abstract: Objective.To determine the effects of accidental injury of varying severity on interleukin (IL)-lα, IL-6, IL-8, tumor necrosis factor-α (TNF-α), and endotoxin release.Design.Prospective, multi-unit, longitudinal study.Setting.Emergency Departments and intensive care units of two university hospitals

Improving intensive care: Observations based on organizational case studies in nine intensive care units A prospective, multicenter study

Abstract: Objective:To examine organizational practices associated with higher and lower intensive care unit (ICU) outcome performance.Design:Prospective multicenter study. On-site organizational analysis; prospective inception cohort.Setting:Nine ICUs (one medical, two surgical, six medical-surgical) at five

Neurologic complications of critical medical illnesses.

Abstract: ObjectivesTo identify the neurologic complications of critical medical illnesses, and to assess their effect on mortality rates and on medical ICU and hospital lengths of stay.DesignProspective clinical evaluation of all medical ICU admissions for 2 yrs.SettingA 14-bed, general medical intensive and

Free radicals and antioxidants in sepsis

Abstract: Objectives: The clinical condition of sepsis is caused by the release of numerous mediators from many cells. The purpose of this review is to describe the results of studies in which the role of free radicals and/or the potential therapeutic value of antioxidants are assessed. Data Sources: The studies described in this review come from a variety of sources, including Med-Line CD-ROM computerized database, Index Medicus, and references identified from the bibliographies of pertinent articles and books. Reports were confined to English language articles from 1966 to 1992. Study Selection: All retrieved references in which free-radical activity was assessed or antioxidants were measured or administered in sepsis or endotoxemia were included. This selection process encompassed clinical, animal and in vitro cell culture work. Data Extraction: Cited literature was found in reputable peer-reviewed clinical or basic science journals. Data Synthesis: Any contradictions in the results of studies are discussed. Conclusions: There is evidence that free radicals play an important role in the pathogenesis of sepsis. Antioxidant therapy has the potential to protect against such injury. It is suggested that combination therapy, which augments the endogenous antioxidant defenses, is likely to be the best approach. (Crit Care Med 1993; 21:1770–1776)

L-arginine pathway in the sepsis syndrome.

Abstract: ObjectiveTo investigate the role of nitric oxide in the regulation of vascular tone in patients with the sepsis syndrome.DesignProspective, intervention study.SettingTertiary care hospital.PatientsFifteen patients admitted to our medical intensive care unit with the diagnosis of sepsis syndrome by d

Influence of long-term oro- or nasotracheal intubation on nosocomial maxillary sinusitis and pneumonia: results of a prospective, randomized, clinical trial.

Abstract: Objective To compare the occurrence rate of nosocomial maxillary sinusitis and pneumonia in patients who have undergone nasotracheal vs. orotracheal intubation. Design Randomized, clinical trial. Setting General adult intensive care unit (ICU) in a nonteaching public hospital. Patients A total of 300 (209 male, 91 female) patients were included. The mean age was 59 +/- 17 (SD) yrs. The simplified acute physiologic score was 14 +/- 6. Reasons for admission to the ICU were: coma (n = 78), pneumonia (n = 46), infection (n = 35), surgery (n = 34), multiple trauma (n = 20), head trauma (n = 12), other (n = 75). Among the 300 patients, 149 were randomized into the nasotracheal group and 151 into the orotracheal group. No statistical difference was found between initial characteristics of the two groups. Interventions Patients were randomized between nasal and oral endotracheal intubation. Gastric intubation was performed via the same route as endotracheal intubation. Sinus computed tomography (CT) scans were performed every 7 days or earlier in case of fever and/or purulent nasal discharge. Criteria for nosocomial sinusitis were as follows: fever of > 38 degrees C, radiographic (sinusal air-fluid level or opacification on CT scan) signs and presence of purulent aspirate from the involved sinus puncture with 10(3) colony-forming units (cfu)/mL. Diagnosis of pneumonia was based on classical criteria and a protected brush specimen with 10(3) cfu/mL. Measurements and main results Radiographic evidence of sinusitis was observed in 78 patients, 45 from the nasal group and 33 from the oral group (p = .08, log-rank test). Among these patients, 54 fulfilled the sinusitis criteria stated above, 29 in the nasal group and 25 in the oral group (p = .75, log-rank test). Nosocomial pneumonia was observed in 26 patients, 17 in the nasal group and 9 in the oral group (p = .11, log-rank test). A multivariable analysis considering sinusitis as a time-dependent factor has suggested that sinusitis increased the risk of nosocomial pneumonia by a factor of 3.8. Nosocomial septicemia was observed in 33 patients, 22 episodes in the nasal group and 13 episodes in the oral group (p = .11, log-rank test). Overall mortality rate was 37% in the nasal group vs. 41% in the oral group (p = .37, log-rank test). Episodes of atelectasis and accidental extubations, and doses of sedative drugs and antibiotics were not different between the two groups. Length of mechanical ventilation did not differ between the two intubation groups. The mean length of stay in the ICU was 11 +/- 15 days in the nasal group vs. 9.5 +/- 11 days in the oral group (p = .27, Student's t-test). Conclusions In patients undergoing prolonged mechanical ventilation, there was no statistically significant difference in the occurrence rate of nosocomial sinusitis or pneumonia between patients undergoing tracheal intubation via the nasal vs. oral route. A trend (p = 0.008) suggests less sinusitis in the orotracheal group.

Oxygen consumption and resting metabolic rate in sepsis, sepsis syndrome, and septic shock

Abstract: ObjectiveTo test the hypothesis that variations in oxygen consumption (Vo2) and resting metabolic rate reflect the severity of bacterial infections and reflect the development of sepsis syndrome and septic shock.DesignObservational study with sequential measurements of Vo2 and resting metabolic rate

Accurate placement of central venous catheters: a prospective, randomized, multicenter trial.

Abstract: Objectives a) To define the frequency of dangerous (intracardiac) central venous catheter placement in a multicenter study of large community hospital intensive care units (ICUs) and to evaluate physician responses to this finding. b) To validate right atrial electrocardiography as a technique to assure adherence with recent Food and Drug Administration (FDA) guidelines regarding the location of central venous catheter tips. c) To conduct a literature review of vascular cannulation and its associated potentially lethal complications. Design Prospective, randomized, blinded, multicenter study. Setting Multidisciplinary ICUs in five large community teaching hospitals. Patients Consecutive patients (n = 112) who required a central venous catheter by either internal jugular vein or subclavian vein at four separate hospitals were assessed using 30-cm catheters. Consecutive patients (n = 50) in a fifth hospital who subsequently required a central venous catheter via the internal jugular vein or subclavian vein route were prospectively randomized to receive a 20-cm central venous catheter with either conventional surface-landmark guidance, or with the right atrial electrocardiography-guided technique. Main Outcome Measures a) Occurrence rate of malpositioned central venous catheters. b) Ability of right atrial electrocardiography to aid in the accurate placement of central venous catheters. Results a) Using conventional placement techniques with a 30-cm catheter, 53 (47%) of 112 initial central venous catheter placements resulted in location of the catheter tip within the heart. Catheter tips were not repositioned to locations outside the right atrium after this finding was identified on initial postprocedure films. b) Using the right atrial electrocardiography technique to place 20-cm central venous catheters resulted in no catheter tip locations within the heart (0/25) vs. 14 (56%) of 25 (p Conclusions a) The FDA guidelines regarding catheter tip location (catheter tip should not be in the right atrium) have not been widely publicized. b) The average safe insertion depth for a central venous catheter from the left or right internal jugular vein or subclavian vein is 16.5 cm for the majority of adult patients; a central venous catheter should not be routinely inserted to a depth of >20 cm. Catheters longer than this size are rarely needed, and potentially dangerous. Catheter tip location is important to document following central venous catheter insertion. Thirty-centimeter central venous catheters should not be used when accessing the central circulation via internal jugular or subclavian veins. c) Right atrial electrocardiography is a technique that assures initial tip position outside the heart in accordance with FDA guidelines. This technique would virtually eliminate the major risk of death (i.e., cardiac perforation) associated with this procedure. d) Recently available, 15− and 16-cm central venous catheters have significant potential to minimins

Treatment of gram-negative septic shock with an immunoglobulin preparation: a prospective, randomized clinical trial.

Abstract: Objective:To evaluate the effectiveness of a polyclonal immunoglobulin (Ig) preparation containing IgG, IgM, and IgA as an adjunctive therapy for septic shock.Design:Prospective, randomized clinical trial.Setting:A clinical immunology ward at the center for internal medicine in a university hospital

Perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome : A prospective, randomized, controlled study.

Abstract: OBJECTIVE To determine the efficacy of perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome. DESIGN Prospective, randomized, controlled study. SETTING State University of New York at Buffalo, School of Medicine and Biomedical Sciences. SUBJECTS Eleven premature lambs with respiratory distress syndrome, delivered by cesarean section. INTERVENTIONS Five lambs were supported by conventional mechanical ventilation alone. Six lambs were switched to perfluorocarbon-associated gas exchange after 60 to 90 mins of conventional mechanical ventilation. Perfluorocarbon-associated gas exchange was accomplished by instilling a volume of liquid perfluorocarbon equivalent to normal functional residual capacity (30 mL/kg) into the trachea, performing 3 to 4 mins of tidal liquid ventilation, and, at end-expiration, with liquid functional residual capacity of 30 mL/kg remaining in the lung, reconnecting the animal to the volume ventilator for gas tidal volumes. MEASUREMENTS AND MAIN RESULTS Serial arterial blood gases and lung mechanics were measured. While receiving conventional ventilation, all animals developed progressive hypoxemia, hypercarbia, and acidosis. However, in the perfluorocarbon-associated gas exchange group, within 5 mins of the initiation of perfluorocarbon-associated gas exchange, mean PaO2 increased four-fold, from 59 +/- 6 torr (7.9 +/- 0.8 kPa) during conventional ventilation to 250 +/- 28 torr (33.3 +/- 3.7 kPa; p < .05) during perfluorocarbon-associated gas exchange, and this increase was sustained at 60 mins of perfluorocarbon-associated gas exchange (268 +/- 38 torr; 35.7 +/- 5.1 kPa; p < .05). Mean PaCO2 decreased progressively from 62 +/- 4 torr (8.3 +/- 0.5 kPa) during conventional ventilation to 38 +/- 3.3 torr (5.1 +/- 0.4 kPa) at 60 mins of perfluorocarbon-associated gas exchange (p < .05). Mean pH concomitantly increased. Dynamic compliance increased three-fold within 15 mins of instituting perfluorocarbon-associated gas exchange, from 0.31 +/- 0.02 mL/cm H2O during conventional ventilation to 0.90 +/- 0.11 mL/cm H2O during perfluorocarbon-associated gas exchange, and this increase was sustained at 60 mins of perfluorocarbon-associated gas exchange (p < .05). Mean peak expiratory flow and mean expiratory resistance were essentially unchanged during perfluorocarbon-associated gas exchange as compared with conventional ventilation in the same group. CONCLUSIONS We conclude that perfluorocarbon-associated gas exchange, which employs liquid functional residual capacity and gas tidal volumes delivered by a conventional ventilator, can facilitate oxygenation and CO2 removal, and dramatically improve lung mechanics in the premature lamb with respiratory distress syndrome.

Impaired β-adrenergic receptor stimulation of cyclic adenosine monophosphate in human septic shock: Association with myocardial hyporesponsiveness to catecholamines

Abstract: ObjectivesTo determine whether myocardial hyporesponsiveness to administered catecholamines occurs in human sepsis and whether this phenomenon is associated with impaired β-adrenergic receptor stimulation of cyclic adenosine monophosphate.DesignProspective study.SettingMedical ICU in a university ho

Intratracheal perfluorocarbon administration combined with mechanical ventilation in experimental respiratory distress syndrome: dose-dependent improvement of gas exchange.

Abstract: OBJECTIVES To test the efficacy of intratracheal instillation of a perfluorocarbon, combined with conventional mechanical ventilation, as well as to establish the dose response of this application on pulmonary parameters in adult animals with acute respiratory failure. DESIGN Prospective, randomized, placebo-controlled study. SETTING Anesthesiology laboratory of a university. SUBJECTS Twelve, adult male New Zealand rabbits. INTERVENTIONS After inducing respiratory failure by repeated lung lavage with saline, one group of animals was treated with perfluorocarbon, while another group was treated with saline to serve as controls (n = 6 per group). Treatment consisted of intratracheal instillation of incremental doses of 3 mL/kg of each liquid up to a total volume of 15 mL/kg. Animals were mechanically ventilated for 15 mins after each treatment dose with volume-controlled ventilation, a tidal volume of 12 mL/kg, frequency of 30 breaths/min, FIO2 of 1.0, and a positive end-expiratory pressure of 6 cm H2O. MEASUREMENTS AND MAIN RESULTS Arterial blood gases and lung mechanics were determined. In the perfluorocarbon group, PaO2 increased with increases in dosage from 75 +/- 15 to 420 +/- 27 torr (10.0 +/- 2.0 to 55.9 +/- 3.6 kPa); PaCO2 decreased from 49 +/- 6 to 43 +/- 5 torr (6.5 +/- 0.8 to 5.7 +/- 0.6 kPa) after the first dose, and remained stable thereafter. Airway pressures were significantly lower after treatment compared with pretreatment values. CONCLUSION The remarkable improvements in pulmonary parameters suggest that this type of ventilatory support offers an effective and simple method of perfluorocarbon application in acute respiratory failure.

Vasoactive mediators and splanchnic perfusion

Abstract: Objective To provide an overview of the splanchnic hemodynamic response to circulatory shock. Data Sources Previous studies performed in our own laboratory, as well as a computerassisted search of the English language literature (MEDLINE, 1966 to 1991), followed by a selective review of pertinent articles. Study Selection Studies were selected that demonstrated relevance to the splanchnic hemodynamic response to circulatory shock, either by investigating the pathophysiology or documenting the sequelae. Article selection included clinical studies as well as studies in appropriate animal models. Data Extraction Pertinent data were abstracted from the cited articles. Results of Data Synthesis The splanchnic hemodynamic response to circulatory shock is characterized by a selective vasoconstriction of the mesenteric vasculature mediated largely by the renin-angiotensin axis. This vasospasm, while providing a natural selective advantage to the organism in mild-to-moderate shock (preserving relative perfusion of the heart, kidneys, and brain), may, in more severe shock, cause consequent loss of the gut epithelial barrier, or even hemorrhagic gastritis, ischemic colitis, or ischemic hepatitis. From a physiologic standpoint, nonpulsatile cardiopulmonary bypass, a controlled form of circulatory shock, has been found experimentally to significantly increase circulating levels of angiotensin II, the hormone responsible for this selective splanchnic vasoconstriction. Conclusions While angiotensin II has been viewed primarily as the mediator responsible for the increased total vascular resistance seen during (and after) cardiopulmonary bypass, it may also cause the disproportionate decrease in mesenteric perfusion, as measured in human subjects by intraluminal gastric tonometry and galactose clearance by the liver, as well as the consequent development of the multiple organ failure syndrome seen in 1% to 5% of patients after cardiac surgery. (Crit Care Med 1993; 21:S55-S68)