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Critical care medicine: An annotated bibliography of the recent literature
The Literature
of Emergency
Medicine
CriticalCareMedicine: An Annotated Bibliography of the Recent Literature GARRET
E. FOULKE,
MD, TIMOTHY
E. ALBERTSON,
MD, PHD
CARDIOVASCULARCRITICAL CARE Wide QRS tachycardia in the conscious adult: Ventricular tachycardia is the most frequent cause. Steinman R, Herrera C, Schuger C, et al. JAMA 1989;261:1013-1016. This study reports 20 consecutive cases of regular wide QRS tachycardia referred to an arrhythmia service. In this series, the tachycardia was commonly (and mistakenly) felt to be supraventricular in origin because the patients remained conscious and their symptoms had been sustained for a mean of 4.8 hours before evaluation. The diagnosis of ventricular tachycardia was established in 17 of the 20 cases. The authors cite their data as refuting the notion that hemodynamically tolerated tachycardias with rates >200 are generally supraventricular in origin. The referral pattern of their specialty service may play some role in biasing the data. Nevertheless, the point is well taken that we should all strive to suspect the more life-threatening ventricular tachycardia regardless of the patient’s hemodynamic or mental status. Diagnosis of acute myocardial infarction by mdhun-111 antlmyosm antibodies and correlation with the traditional techniques for the evaluation of extent and localization. Volpini M, Giubbini R, Gei P, et al. Am J Cardiol 1989;63:7-13. This study of 57 patients found that myocardial scanning with indium-111 antimyosin antibodies was 98% sensitive and 85% specific for diagnosis of acute myocardial infarction. In addition, the technique had good concordance with other techniques for topographic localization of infarct. It appears to be a reliable method for detection and localization of infarct. Although far from routine, this procedure may someday be highly useful in certain situations where the standard techniques may be unreliable.
From the Divisions of Emergency Medicine/Clinical Toxicology and Pulmonary/Critical Care Medicine, Department of Internal Medicine, University of California Davis Medical Center, Sacramento. Address reprint requests to Dr Foulke: Division of Emergency Medicine/Clinical Toxicology, University of California Davis Medical Center, 2315 Stockton Blvd, Sacramento, CA 95817. 0 1989 by W.B. Saunders Company. 0735-8757/89/0705-0012$5.00/O 550
A randomized controkd trial of hospital discharge three days after myocardial infarction in the era of reperfusion. Top01 E, Burek K, O’Neill W, et al. N Engl J Med 1988;318: 1083-1088. Five hundred seven consecutive patients were screened; 179 of them were felt to have uncomplicated myocardial infarction. After early exercise testing, 80 patients with no provocable myocardial ischemia were randomly assigned to discharge on day 3 or discharge on day 7 to 10. Seventy-six of these patients had received coronary reperfusion therapy. The patients had at least 6 months of follow-up, and no deaths were reported in either group. Rate of hospital readmissions, reinfarctions, and angina were similar in both groups. Hospital charges were obviously significantly less in the early-discharge group. The authors call for a more largescale trial of the safety of early hospital discharge. As the era of cost containment and myocardial reperfusion merge, we may be seeing a more rapid turnover of uncomplicated myocardial infarction patients. This has obvious implications for the potential emergency department “reevaluation” visits of such patients. Thrombolytic therapy: Current status (part 1). Marder Sherry S. N Engl J Med 1988;318:1512-1520.
V,
Thromholytic therapy: Current status (part 2). Marder Sherry S. N Engl J Med 1988;318:1585-1595.
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Unresolved clinical pharmacologic questions in thromholytic therapy for acute myocardial infarction. Sherry S. J Am Co11 Cardiol 1988;12:519-525. A symposium: Silent myocardial lschemla and lnfarctionPast, present and future. Lauler D (ed). Am J Cardioll988; 61(12). Considerable literature on thrombolytic therapy and silent myocardial ischemia has been published recently. Space does not permit the review of all pertinent articles. The above review articles are a good place to start for recent events and current concepts. In regard to thrombolytic therapy, the author of the third article in this list says, “Review of the available data raises serious questions as to the validity of current views and the appropriateness of prevailing trends.”
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CRITICAL CARE TRANSPORT Feasibility and safety of emergency interhospital transport of patients during early hours of acute myocardial infarction. Gore J, Corrao J, Goldberg R, et al. Arch Intern Med 1989; 149:353-355. Identification and transport of patients with acute myocardial infarction for thromholytic therapy. Bumey R, Walsh D. Ann Emerg Med 1988;17:1158-1165. Reperfusion arrhythmia: Myth or reality? Bumey R, Walsh D, Kaplan L, et al. Ann Emerg Med 1989;18:240-243. The first article is a prospective analysis of 57 patients transported by ground or air. Before transport, 81% of patients were having chest discomfort, 23% were hypotensive, and 21% had high-grade ventricular ectopy or nonsustained ventricular tachycardia. During transport, 72% continued to have chest discomfort; however, only 4% were hypotensive. Nine percent continued to have arrhythmias, but their instability was considered noncritical. The occurrence of these complications in transport did not appear to be related to distance traveled or mode of transportation, but this was not studied rigorously. All patients survived and 93% were eventually discharged. The authors conclude that the rapid referral and transport of these patients for definitive care at their tertiary care facility has significant benefit and that the transport can be undertaken safely. They point out that it is impossible to estimate what the outcome would have been if the patients had remained at their referring hospitals, but note that current studies suggest that rapid therapeutic coronary intervention may have a significant impact on the patients’ health care. In the second and third articles, the experience at another major center is reviewed, with conclusions similar to those of the fist article. Defibrillation safety in emergency helicopter transport. Dedrick D, Darga A, Landis D, et al. Ann Emerg Med 1989; 18:69-71. Defibrillation in the close-quarter metallic environment of the helicopter has been a significant concern to transport teams. This study used a test model in the helicopter environment and found that a maximum of 1.5 mA of transient leakage occurred with a standard battery-powered defibrillator. This is well within the accepted safety standard of 50 mA. In-flight tests revealed no interference with avionics or medical equipment and adequate clearance for medical personnel. A survey of flight programs revealed that 87% of 69 programs had defibrillated in the air without hesitation or complications. Another 10% had not had to defibrillate in the aircraft. Only 2.5% of programs flew aircraft that they felt were too small to allow safe defibrillation. Pediatric critical care transport: Is a physician always needed on the team? McCloskey K, King W, Byron L. Ann Emerg Med 1989;18:247-249. This study reviewed drugs used, procedures performed, and questionnaires given to the flight crew to assess when a physician seemed necessary on a pediatric critica care transport team. In 46%, a physician was deemed to be not necessarily required for the transport’s success. The group
concludes that it may not always be necessary to send a physician as part of a critical care transport team. The problem is that despite being able to identify some flights retrospectively that did not require a physician in transport, there are no data cited that pertain to how one would prospectively identify the need for a physician. By their own data, the authors show that the environment is such that a physician would be needed >50% of the time. This would therefore mean that if a physician were not sent, the odds would be high that the physician would be needed and not available. It seems one could easily draw the conclusion that a physician should always be on the pediatric critical care transport team in view of the very high likelihood of being needed.
GASTROINTESTINAL Prophylactic sclerotherapy before the first episode of variceal hemorrhage in patients with cirrhosis. Sauerbruch T, Wotzka R, Kopcke W. N Engl J Med 1988;319:8-15. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices: A prospective multicenter study. North Italian Endoscopic Club. N Engl J Med 1988;319:983-989. The issue seems settled that sclerotherapy is the appropriate treatment for active variceal bleeding. An ancillary question has been what to do when endoscopy is undertaken and diagnoses varices that are not the active bleeding site at the time. In the first study, 133 patients at several German health centers were randomly assigned, with 68 receiving prophylactic sclerotherapy and 65 receiving no prophylaxis. The incidence of bleeding and the mortality rate during a 22month mean follow-up period was slightly lower in the prophylaxis group, but not significantly so. The authors conclude that overall, prophylactic sclerotherapy does not significantly reduce either of these phenomena. They did identify a subgroup of patients with moderately decompensated (Child class 8) alcoholic cirrhosis who may benefit from prophylactic sclerotherapy by reduction of the incidence of bleeding. In the second study, 321 patients in Italian centers were studied to identify whether clinical features and appearances of the varices could identify those at highest risk for bleeding. Patients were followed in the study for up to 38 months; during this time 85 patients had episodes of bleeding. The authors found that the prognostic index using the Child’s classification, the size of the varices, and the presence of certain markings on the varices was significantly related to the risk of bleeding. They conclude that the prognostic index can be used to identify candidates for prophylactic treatment.
GENERAL The therapeutic efficacy of critical care units: Identifying subgroups of patients who benefit. Ron A, Aronne L, Kalb P. Arch Intern Med 1989; 149:338-341. Impact of critical care physician &&lug on patients with septic shock in a university hospital medical intensive care unit. 551
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Reynolds H, Haupt M, Thill-Baharozian 1988;260:3446-3450. Outcomes in critical 1988;260:3487.
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Together these three articles further emphasize and focus on the efficacy of critical care medicine. The first report defines a subgroup of patients that had an improved outcome based on survival stratified by severity of illness and stability. The general category that showed improved outcome was the group of unstable patients with moderate illness. None of three remaining categories (stable, not ill; stable, moderately ill; and unstable, severely ill) showed significant benefit from direct critical care unit admissions. This study begins to examine a multitude of factors that may help predict at the time of admission which patients should be directly admitted to critical care units. The retrospective study of Reynolds et al compares two consecutive 1Zmonth periods: one in which faculty without specific critical care medicine training supervised a medical intensive care unit and one in which physicians with critical care medicine training supervised the same unit. Patients’ acute physiology and chronic health evaluation scores were similar during the two periods; however, the mortality was significantly lower during the critical care medicine-supervised period. The frequency of use of mechanical ventilation was not significantly different, but invasive procedures such as pulmonary artery catheters and systemic arterial catheters were used more frequently during the period in which faculty formally trained in critical care medicine supervised. The suggestion of this study is that formal training in critical care medicine can improve the survival rate of patients. In his editorial, Dr Bone comments on the need for reexamination of the reimbursement schemes for critical care medicine based on severity of illness. He also calls for more ethical, legal, and economic research into critical care medicine and recognition of “centers of technology in critical care medicine.” Patients’ and families’ preferences for medical intensive care. Danis M, Patrick D, Southerland L, et al. JAMA 1988; 260:797-802;839-840. This study used a retrospective survey technique of patients aged 255 years who had experienced previous medical intensive care unit hospitalizations in a university teaching hospital. Family members were interviewed if the patient had died during the hospital stay. Interestingly enough, 70% of patients and families were 100% willing to undergo intensive care therapy again to achieve even 1 month of survival. Only 8% were completely unwilling to undergo intensive care unit treatment again to achieve prolonged survival. The preferences for this were poorly correlated with functional status or quality of life and were not altered by life expectancies for the majority of the respondents. Similarly, age, severity of critical illness, length of stay, and charges for previous intensive care unit stays did not influence the patients’ willingness to undergo additional intensive care unit experiences. Together these data suggest that families are not negatively influenced by one previous intensive care unit experience and that realistic expectations of the future are not likely to play an important role in patient- or family552
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motivated choices for future use of limited health care resources in the intensive care unit setting.
HEMOOYNAMIC MONITORING Bedside catheterization of the pulmonary artery: Risks compared with benefits. Matthay M, Chatterjee K. Ann Intern Med 1988;109:826-834. The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. Stevenson L, Perloff J. JAMA 1989;261:884-888. Cardiac output changes and continuous mixed venous oxygen saturation measurement in the critically ill. Vaughn S, Puri V. Crit Care Med 1988;16:495-498. The pulmonary artery catheter: The debate continues. Sibbald W, Sprung C. Chest 1988;94:899-901. The first article outlines the relative risks and benefits of using pulmonary artery catheters in critically ill patients. It reviews the theoretical and practical applications of the device. Guidelines and alternatives to the pulmonary artery catheter are discussed. The study by Stevenson and Perloff prospectively examined physical signs of congestive heart failure and compared them with the hemodynamic measurements obtained from the Swan-Ganz catheter in 50 patients with known chronic heart failure. Rales, edema, and elevated mean jugular venous pressure were absent in 18 of 43 patients with markedly elevated pulmonary capillary wedge pressures. These signs of congestive heart failure had a 58% sensitivity and 100% specificity in this group. They concluded, as has been the experience of many before, that physical examinations are not reliable in chronic failure in all patients, and in many patients may result in inadequate therapy. The article by Vaughn and Puri examined 46 patients admitted to a critical care unit. They examined the efficacy of a pulmonary artery catheter that gives fiberopticmeasured continuous measurement of mixed venous O2 saturation. Patients with this catheter were nonrandomly compared with a group in which standard pulmonary artery catheters were inserted. Patients were suffering from acute myocardial infarction, cardiogenic shock, or respiratory failure or needed preoperative hemodynamic monitoring. The authors were unable to document any particular clinical value to continuous monitoring of the mixed venous 0, saturations. Further, they were unable to use the measurement as an early predictor of cardiac output changes, drawing into question the value of this expensive device. The final editorial by Sibbald and Sprung reexamined the controversy ignited by articles by Gore et al and Robin that appeared in Chest in 1987. It provides interesting reading and a lively summary of the current controversies surrounding pulmonary artery catheter use.
IATROGENESIS An attachable silver-impregnated cuff for prevention of infection with central venous catheters: A prospective randomized multicenter trial. Maki D, Cobb L, Garman J, et al. Am J Med 1988;85:307-314.
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A novel silver-impregnated attachable cuff was used to reduce signticantly the catheter-related infections from percutaneously inserted central venous lines. Patients were randomly assigned to central venous lines with or without the silver-impregnated cti. A significant reduction in catheter colonization (28.9% v 9.1%) and bacteremia (3.7% v 1.O%) occurred with the use of this cuff. Prospective study of catheter-related infection during prolonged arterial catheterization. Norwood S, Cormier B, McMahon N, et al. Crit Care Med 1988;16:836-839. Fifty-six surgical intensive care unit patients were prospectively studied using 96 arterial catheters from 75 different anatomical sites. Every 96 hours, all catheters were semiquantitatively cultured and the entry sites were swabbed and cultured. It was concluded that arterial catheter-related infections develop in < 10% of radial and femoral sites, even when these catheters are used for >96 hours. The majority of radial and femoral arterial sites (90%) remained clear for long periods, particularly when the percutaneous colonization sites were controlled. This study also suggests that skin site swab cultures may be useful in determining when arterial catheters should be removed and semiquantitatively cultured. Prevention of colonization and infection in critically ill patients: A prospective randomized study. Kerver A, Rommes J, Mevissen-Verhage E, et al. Crit Care Med 1988;16:10871093. Effects of gastric alkalization on bacterial colonization in critically ill patients. Garvey B, McCambley J, Tuxen D. Crit Care Med 1988;17:211-216. These two clinical investigations provide increasing evidence that gram-negative bacteria counts are altered in critically ill patients. In the study by Kerver et al, attempts were directed at reducing the bacterial load of critically ill patients by treating a randomized group with nonabsorbable antimicrobial agents including tobramycin, amphotericin B, and polymyxin E. In addition, these patients received parenteral cefotaxim for five to seven days. Compared with the nontreated control group, significantly fewer episodes of nosocomial infections and resulting mortality occurred. In the study by Garvey et al, the effect of gastric alkalization on critically ill patients was examined. All 25 patients received antacids every 12 hours, and 15 of 25 received additional HZ-receptor antagonists. They then underwent nasogastric, urine, and tracheal secretion culturing on a regular basis. Many were receiving systemic antibiotic therapy. It was demonstrated that colonization occurs despite concurrent appropriate antibiotics, and that this colonization is universal in alkalinized gastric solutions. This study was limited in its scope because no control group was monitored without gastric alkalinization therapy to determine whether this process is simply secondary to the effect of alkalinization of the gastric secretions or to the degree of illness.
INFECTIOUS DISEASE Treatment of gram-negative septic shock with human IgG antibody to Escheriehio coli J5: A prospective, double-blind,
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randomized trial. Calandra T, Glauser M, Schellekens J, et al. J Infect Dis 1988;158:312-319. Phase I study of a murine monoclonal anti-lipid A antibody in bacteremic and nonhacteremic patients. Harkonen S, Scannon P, Mischak R, et al. Antimicrob Agents Chemother 1988;32:710-716. There has been a burgeoning effort to find an antidote to gram-negative endotoxin via use of antibody to the J5 antigen. This Escherichia coli antigen is felt to be shared by many gram-negative endotoxin molecules. The fust article studied 100 patients, 71 of whom had documented gramnegative infections. A human immunoglobulin against J5 antigen was compared with a standard pooled immunoglobulin preparation. This study found that there was no difference in the number of systemic complications of shock and no difference in mortality. The second studied a similar but murine monoclonal antibody in nine patients. This preliminary study demonstrated that the preparation appeared to be well tolerated. At the higher dosage range, however, the murine antibody may well be immunogenic. Large-scale controlled trials of both human and murine monoclonal antibodies are underway at present. It is hoped that these large-scale trials will demonstrate a therapeutic benefit to the use of this compound. Dexamethasone therapy for bacterial meningitis: Results of two double-blind, placebo-controlled trials. Lebel M, Freij B, Syrogiannopoulos G, et al. N Engl J Med 1988;319:964971. This article reports the combined results of two prospective placebo-controlled trials using dexamethasone therapy in infants and older children with bacterial meningitis. The study found similar mortality rates but more rapid reversal of CSF values in the dexamethasone-treated group. The significant differences between the groups was that the dexamethasone-treated group became afebrile earlier and had a lower incidence of sensorineural hearing loss. On the basis of these data, the authors conclude that dexamethasone should be routinely administered during the first four days of antimicrobial therapy in infants and children. Acyclovir-resistant herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. Erlich K, Mills J, Chatis P, et al. N Engl J Med 1988;320:293-2%. Resistance to antiviral drugs: The end of innocence. Hirsch M, Schooley R. N Engl J Med 1988;320:313-314. The titles of this report and the accompanying editorial are almost self-explanatory. The report describes 12 patients with acquired immunodeficiency syndrome (AIDS) over a 2!&year period who developed acyclovir-resistant herpes infections. The likely setting for ongoing problems with acyclovir-resistance is the AIDS population. However, unjudicious use of acyclovir will presumably result in increasing frequency of resistance to antiviral drugs. We must therefore concern ourselves with judicious use of such agents in the hopes of prolonging the point when we see multiply resistant viruses just as we see many highly resistant bacteria in the modern era. 553
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NEUROLOGICAL Leftventricular wall motion abnormalities in subarachnoid hemorrhage: An echocardlographic study. Pollick C, Cujec B, Parker S, et al. J Am Co11 Cardiol 1988;12:600-605. Increased intracranial pressure elicits hypertension, increased sympathetic activity, electrocardiographic abnormalities and myocardial damage in rats. Shanlin R, Sole M, Rahimifar M, et al. J Am Co11 Cardiol 1988;12:727-736. These studies represent further data confirming that neurological lesions can produce cardiac abnormalities. The first study reports on 13 patients, four of whom exhibited left ventricular wall motion abnormalities despite no history of heart disease. Their neurological grades were significantly worse than those without wall motion abnormalities, and all four had T-wave inversions (v one of nine without wall motion abnormalities). These cardiac abnormalities associated with high-neurological-grade subarachnoid hemorrhage are readily detected by the two-dimensional echocardiographic techniques used in this study. The second article reports on 59 rats with experimental intracranial hypertension. The rats were found to have significant increases in plasma catecholamines and areas of focal constriction with microvascular spasm on myocardial histological examination. These observations suggest that myocardial damage and abnormalities noted in intracranial hypertension may result from both of these phenomena. The data are significant in terms of both the management of victims of intracranial hypertension and the implications for organ transplant. Does magnesium sulfate treat eclarnptic seizures? Yes. Dinsdale H. Arch Neurol 1988;45: 1360-1361. No, magnesium sulfate should not be used in treating eclamptic seizures. Kaplan P, Lesser R, Fisher R, et al. Arch Neurol 1988;45:1361-1364. These two articles highlight the controversy over a longaccepted obstetric practice. The authors of the second article argue that standard antiseizure medicines are much better therapy for eclamptic seizures than magnesium. Although they admit that magnesium therapy may have a role in the treatment of preeclampsia, they argue that the risks of magnesium and of standard anticonvulsants are equivalent, whereas magnesium is not as effective an anticonvulsant, or even a proven one.
PHARMACOLOGY Attenuation of acute lung injury in septic guinea pigs by pentoxifylline. Ishizaka A, Wu Z, Stephens K, et al. Am Rev Respir Dis 1988;138:376-382. Pentoxlfylline improves survival following hemorrhagic shock. Coccia M, Waxman K, Soliman H, et al. Crit Care Med1989;17:36-38. Pentoxifylhne decreases endotoxin-induced pulmonary neutrophil sequestration and extravascular protein accumulation in the dog. Welsh C, Lien D, Worthen S, et al. Am Rev Respir Dis 1988;138:1106-1114. 554
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ARDS, neutrophlls, and pentoxifylllne. Mandell G. Am Rev Respir Dis 1988;138: 1103-l 104. Pentoxifylline is a drug approved for use in claudication and other peripheral vascular circulation problems. It is a methylxanthine that increases intracellular cyclic AMP. These three studies demonstrate a marked reduction in lung injury with pentoxifylline in models of shock. The first study used E coli injected in guinea pigs with constant pentoxifylline infusion before exposure. Similarly, in the third study pentoxifylline was demonstrated to decrease neutrophil pulmonary accumulation and prevent increases in pulmonary vascular permeability to proteins induced by salmonella endotoxin in dogs. When pentoxifylline was added to ringers solution in the resuscitation of rats after hemorrhagic shock, significant improvement in survival was demonstrated. The final editorial discusses possible mechanisms of pentoxifylline action in these shock conditions. The possibility that pentoxifylline interacts with the inflammatory cytokines, either by decreasing production of tumor necrosis factor and interleukin-1 or by stabilizing phagocytes and other cells, is cited. Together, these data suggest that pentoxifylline or derivatives of pentoxifylline may be important in the shock resuscitation of the future. The effects of midazolam reversal by RO 15-1788 on cerebral perfusion pressure in patients with severe head injury. Chiolero R, Ravussin P, Anderes J. Intensive Care Med 1988; 14: 196-200. The benzodiazepine antagonist RO 15 1788 (flumazenil) is currently being evaluated for potential use in the United States. This study examines the effects of reversing midazolam sedation in 15 patients with severe head injuries (Glasgow coma scale ~8). Those patients who had poor control of intracranial pressure (ICP) before receiving the benzodiazepine antagonist had a significant increase in ICP after reversal of the midazolam. Those patients with good control of ICP before treatment with the benzodiazepine antagonist had no significant change in ICP. Arousal after midazolam reversal was obvious in five patients, who were then quickly extubated. This study suggests that while the benzodiazepine antagonist may well have an important role in headinjured patients, great care must be exercised because it can exacerbate elevated or poorly controlled ICP. Propylene glycol-induced side effects during intravenous nitroglycerin therapy. Denney H, Daelemans R, Verpooten G, et al. Intensive Care Med 1988;14:221-226. This important study reviews 28 consecutive patients who received intravenous nitroglycerin for acute myocardial infarctions or preload reduction. The intravenous doses and durations of therapies ranged from 0.5 to 6 &kg per minute of nitroglycerine for 1 to 12 days. Propylene glycol is used as a solvent for a large number of drugs including some intravenous nitroglycerine preparations. In this study, 10.5% of the patients had evidence of acute hemolysis. Hemoglobinuria was present in 3.5% of the cases. Serum osmohdity increased by 54 mosmlkg with the nitroglycerine infusion. Together these data suggest that subtle toxicity from propylene glycol may be a contributing factor to the morbidity
FOULKE AND ALBERTSON H CRITICAL CARE MEDICINE: ANNOTATED BIBLIOGRAPHY
associated with certain nitroglycerine infusion preparations and other drugs that use propylene glycol diluent.
PROCEDURES AND TECHNIQUES
evidence cited in this study suggests that this technique can be used to inactivate endotoxin in the blood with polymyxin B.
RESPIRATORY
Intraosseous infusion of muscle relaxants. Katan B , Olshaker J, Dickerson S. Am J Emerg Med 1988;6:353-354.
An expanded definition of the adult respiratory distress syn-
The authors successfully used an intraosseous line for infusion of succinylcholine chloride, atracurium besylate, and thiopental. This is the first report of such a technique. Although it is a single case report of use in a 6?&month-old, 7.5kg child, it highlights the potential for use of this technique in administering a wider range of emergent drugs in the pediatric age group.
Diagnostic criteria for adult respiratory distress syndrome time for reappraisal. Rocker G, Pearson D, Wiseman M, et al. Lancet 1989;1:120-123.
Emergency flexible fiberoptic nasotracheal intubation: A report of 60 cases. Delaney K, Hessler R. Ann Emerg Med 1988; 17:919-926. Use of flexible fiberoptic endoscopy for determination of endotracheal tube position in the pediatric patient. Dietrich K, Strauss R, Cabalka A, et al. Crit Care Med 1988;16:884887. The first article reports a series of 60 patients in which emergency flexible fiberoptic nasotracheal intubation failed in only 13%. There was a 22% incidence of bleeding and a 9% incidence of esophageal intubation. Overall the report highlights at least one center’s successful use of the technique for difficult intubations. In high-acuity (particularly trauma) centers, the technique should probably become more widely used. The second article documents the utility of the fiberoptic technique for determining proper endotracheal tube placement. The only difference between this technique and the use of a chest radiograph for tube placement was time differential (mean, 40 seconds v 30.6 minutes, respectively). The only complicating feature is the presence of copious secretions. Otherwise this is a rapid, highly reliable, safe, and highly useful technique. Placement of multiorlficed CVP catheters via antecubital veins using intravascular electrocardiography. Artru A, Colley P. Anesthesiology 1988;69:132-135.
drome. Murray J, Matthay M, Lute Respir Dis 1988;138:720-723.
J, et al. Am Rev
These two articles offer extensive refinement to the evaluation and definition of the adult respiratory distress syndrome (ARDS). The paper by Murray et al defines a useful lung injury score for evaluating the degree of pulmonary damage in ARDS patients. In addition, a table outlining the characteristics of parenchymal lung injury and further detining this heterogenous group of patients is provided. Rocker et al provide additional diagnostic criteria for ARDS patients. They specifically have examined the continuum of ARDS patients with regards to their hypoxia, plasma elastase complex, and bronchoalveolar iavage protein content. This analysis points out that the condition recognized as ARDS is not a distinct pathophysiological entity but a continuum of lung injury. The prone position in ARDS patients: A clinical study. Langer M, Mascheroni D, Marcolin R, et al. Chest 1988;94:103107. This article examines body position in the ARDS patient. More than 50% of the patients in this study improved their Pao, by at least 10 mmHg after 30 minutes in the prone position. When one of the “responder” patients were compared with a “nonresponder” patient by computerized tomography in the prone and supine positions, posterior basal densities disappeared with appearance of new anterior region densities in both patients. The etiology of the improvement in blood gases was not obvious from this study; however, the realization that ARDS affects the lung tissue in a nonhomogenous manner is certainly brought out. Cold-induced pulmonary oedema in scuba divers and swimmers and subsequent development of hypertension. Wilmshurst P, Nuri M, Crowther A, et al. Lancet 1989;1:62-65.
A past report by these authors regarding the use of a catheter guided by intravascular ECG delineated less than satisfactory success rates and insertion times. The new report contained in this article reveals more satisfactory results with this rather innovative technique. In a very controlled anesthesia setting, the catheter was successfully placed in 58 of 60 patients with a mean time of 6.3 ? 3.6 minutes. This required a total of 91 attempts. This unusual technique might be considered in certain patients (bums, etc) in whom vascular access is difficult in the usual central venous locations.
This article offers an additional etiology of ARDS. The effects of cold water or increased partial pressure of oxygen were examined in 11 divers with a history of pulmonary edema while at-depth or surface swimming. Evidence of cold-induced pulmonary edema and cardiac decompensation was seen in some of these patients. The exact mechanism for this cold-induced pathophysiology is unknown at this time.
New approach to endotoxic and septic shock by means of polymyxin B immobilized fiber. Hanasawa K, Tani T, Kodama M. Surg Gynecol Obstet 1989;168:323-331.
Protection against pulmonary 0, toxicity by N-acetylcysteine. Wagner P, Mathieu-Costello 0, Bebout D, et al. Eur Respir J 1989;2:116-126.
This fascinating study in 12 dogs shows successful treatment of endotoxic shock using hemoperfusion over a fiberous carrier impregnated with polymyxin B. The preliminary
This study of 12 anesthetized dogs exposed to prolonged 100% oxygen demonstrated that N-acetylcysteine, a known antioxidant, protected against oxygen-caused functional and
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structural abnormalities. This study is a prodrome to current clinical studies examining the effectiveness of Nacetylcysteine in ARDS and other lung conditions thought to result from toxic free radicals. Effect of verapamil on pulmonary and eicosanoid responses to endotoxin in awake sheep. Ahmed T, D’brot J, Wasserman M, et al. J Appl Physiol 1988;64:1700-1708. Using the sheep model with E cofi endotoxin, this study demonstrated that pretreatment with verapamil, 150 &kg, followed by continuous infusion of verapamil after endotoxin exposure, blunted the normal increase in lung resistance and decrease in Pao,. At this dose, verapamil pretreatment did not alter endotoxin-induced changes in pulmonary vascular resistance, WBC counts, arterial thromboxane B,, prostaglandin F2_, or 6-ketoprostaglandin F,, concentrations. At higher doses, verapamil demonstrated substantial blunting and attenuation of endotoxin-induced changes in pulmonary hemodynamics, airway mechanics, leukocyte count, and cyclooxygenase metabolites. It may have an important potential therapeutic role in endotoxin-induced lesions. Future clinical trials are needed. Role of brain lactic acidosis in hypoxic depression of respiration. Neubauer J, Simone A, Edelman N. J Appl Physiol 1988;65:1324-1331. This study with anesthetized, paralyzed cats showed that ventral medullary acidosis resulted in greater depression of phrenic nerve activity for any given level of brain hypoxia. Lactic acidosis near the central chemosensitive regions of the midbrain can produce a small stimulation of respirations during progressive brain hypoxia, but the overwhelming response to central lactic acidosis of progressive brain hypoxia is respiratory depression. This pathophysiological finding points to lactic acidosis as a contributing factor to the downhill spiral associated with progressive brain hypoxia.
SHOCK AND RESUSCITATION Hemorrhagic shock induces bacterial translocation from the gut. Baker J, Deitch E, Berg R, et al. J Trauma 1988;28: 8%~903. Endotoxemia and bacteremia during hemorrhagic shock. Rush B, Sot-i A, Murphy T, et al. Ann Surg 1988;207:549-554. Considerable attention has recently been focused on the gastrointestinal tract and the breakdown of normal barriers to bacterial translocation. The first article reports on bacterial translocation to mesenteric lymph nodes, livers, and spleens of rats subjected to hemorrhagic shock. There was a significant correlation between this event and the amount of time of shock. There was no correlation in a sham-operated group. The second article reports on a similar model in 26 rats, with findings of bacteremia and endotoxemia in 50% and 87%, respectively. Also reported are some preliminary findings regarding these same events in severe trauma patients. Although flawed in certain ways, both of these studies suggest a phenomenon that those of us practicing critical care medicine have long suspected. 556
Detection of circulating tumor necrosis factor after endotoxin administration. Michie H, Manogue K, Spriggs D, et al. N Engl J Med 1988;318:1481-1486. Much work has been done on the substance known as tumor necrosis factor and its relationship to the chain of events whereby endotoxin might produce injury and septic shock. This rather adventuresome study looked at levels of tumor necrosis factor (cachectin), interleukin-lB, and gamma interferon in 13 healthy volunteers who were administered E co/i endotoxin. Control levels of cachectin were ~35 pg/mL but increased 90 to 100 minutes after endotoxin to mean peak levels of 240 * 70 pg/mL. Interleukin-l@ and gamma interferon levels did not change. The authors cite these data as evidence that the response to endotoxin is associated with a pulse of cachectin and that the resultant downstream responses are effected through the cyclooxygenase pathway. Human recombinant tumor necrosis factor alpha infusion mimics endotoxemia in awake sheep. Johnson J, Meyrick B, Jesmok G, et al. J Appl Physiol 1989;66:1448-1454. The findings in this study complement the data in the article above. Using the sheep lung lymph tistula model, the authors studied the effect of infusion of tumor necrosis factor on subsequent physiology. Pulmonary artery hypertension, hypoxemia, and peripheral blood and lung lymph leukopenia all occurred during the four hours of the study. These were followed by increases in protein-rich lung lymph flow consistent with an increased microvascular permeability in the pulmonary bed. These changes are all very similar to the changes seen in this model with endotoxin infusion. The authors conclude that tumor necrosis factor induces a response remarkably similar to that of endotoxemia and that it may mediate endotoxin-induced lung injury. Role of endotoxemia in cardiovascular dysfunction and mortality. Natanson C, Danner R, Elin R, et al. J Clin Invest 1989;83:243-251. This is another in a series of studies by the group that has done the most work characterizing cardiovascular dysfunction in sepsis. In this animal study there were 14 control dogs and 74 infected dogs. This study used E coli and Staphylococcus aureus as the bacterial agents. It further characterizes the myocardial depression and cardiovascular changes associated with E coli infection and endotoxemia. Interestingly enough, the S aureus-infected dogs who did not demonstrate any endotoxemia had similar cardiovascular changes. The authors cite these data as evidence that markedly different organisms with and without endotoxin production can incite some common pathway, resulting in the cardiovascular changes seen in sepsis.
VENTILATION Best PEEP: Issues and choices in the selection and monitoring of PEEP levels. Kirby R. Respir Care 1988;33:569-576. Positive end-expiratory pressure: Reduction and withdrawal. Hudson L, Weaver J, Haisch C, et al. Respir Care 1988; 33:613-617.
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The first article (from an issue completely devoted to a symposium on the topic) reviews past and recent studies on how to find the “best” level of positive end-expiratory pressure (PEEP). It seems we have come full circle on this topic. In past years, studies of very high levels of PEEP were published. Some recent studies suggest that the lowest level of PEEP which achieves adequate oxygenation with an FIo, ~50% may be best in both the acute and chronic phases. The second article discusses an interesting subject on which a minimal amount of data are available. Based on the past studies cited and their own work contained in the article, the authors recommend reduction of PEEP by 5 cm H,O at a time with an interval of less than every six hours. They also recommend reduction for a three-minute period and then return to a baseline level while a blood gas analysis is obtained (a so-called three-minute PEEP trial). Their data suggest that patients who go through this short interval of PEEP reduction successfully are likely to be candidates for continued PEEP reduction. Pressure controlled inverse ratio ventilation in severe adult respiratory failure. Tharratt R, Allen R, Albertson T. Chest 1988;94:755-762.
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Clinical trials of some of the more recent ventilatory modalities are now making their way into the literature. This article reports a series of 31 patients receiving inverse-ratio ventilation. Peak inspiratory pressure was reduced from 66 + 2.3 to 48 f 1.6 cm H,O. PEEP was reduced from 15 & 1.0 to 2.5 -+ 0.5 cm H,O. Oxygenation was improved. The authors conclude that inverse-ratio ventilation can be successfully and safely implemented in critically ill patients in a manner such that it provides improved oxygenation at lower minute volume, peak airway pressure, and PEEP requirements. Airway pressure release ventilation (APRV): A human trial. Garner W, Downs J, Stock M, et al. Chest 1988;94:779781. This is an initial report of a human trial of the airway pressure release ventilation (APRV) modality. Fourteen patients undergoing elective coronary operations received conventional ventilation and then were studied with APRV in the postoperative period. The authors conclude that APRV supported oxygenation and ventilation in patients with mild lung injury at much lower peak airway pressures than produced by conventional ventilation.
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CriticalCareMedicine: An Annotated Bibliography of the Recent Literature GARRET
E. FOULKE,
MD, TIMOTHY
E. ALBERTSON,
MD, PHD
CARDIOVASCULARCRITICAL CARE Wide QRS tachycardia in the conscious adult: Ventricular tachycardia is the most frequent cause. Steinman R, Herrera C, Schuger C, et al. JAMA 1989;261:1013-1016. This study reports 20 consecutive cases of regular wide QRS tachycardia referred to an arrhythmia service. In this series, the tachycardia was commonly (and mistakenly) felt to be supraventricular in origin because the patients remained conscious and their symptoms had been sustained for a mean of 4.8 hours before evaluation. The diagnosis of ventricular tachycardia was established in 17 of the 20 cases. The authors cite their data as refuting the notion that hemodynamically tolerated tachycardias with rates >200 are generally supraventricular in origin. The referral pattern of their specialty service may play some role in biasing the data. Nevertheless, the point is well taken that we should all strive to suspect the more life-threatening ventricular tachycardia regardless of the patient’s hemodynamic or mental status. Diagnosis of acute myocardial infarction by mdhun-111 antlmyosm antibodies and correlation with the traditional techniques for the evaluation of extent and localization. Volpini M, Giubbini R, Gei P, et al. Am J Cardiol 1989;63:7-13. This study of 57 patients found that myocardial scanning with indium-111 antimyosin antibodies was 98% sensitive and 85% specific for diagnosis of acute myocardial infarction. In addition, the technique had good concordance with other techniques for topographic localization of infarct. It appears to be a reliable method for detection and localization of infarct. Although far from routine, this procedure may someday be highly useful in certain situations where the standard techniques may be unreliable.
From the Divisions of Emergency Medicine/Clinical Toxicology and Pulmonary/Critical Care Medicine, Department of Internal Medicine, University of California Davis Medical Center, Sacramento. Address reprint requests to Dr Foulke: Division of Emergency Medicine/Clinical Toxicology, University of California Davis Medical Center, 2315 Stockton Blvd, Sacramento, CA 95817. 0 1989 by W.B. Saunders Company. 0735-8757/89/0705-0012$5.00/O 550
A randomized controkd trial of hospital discharge three days after myocardial infarction in the era of reperfusion. Top01 E, Burek K, O’Neill W, et al. N Engl J Med 1988;318: 1083-1088. Five hundred seven consecutive patients were screened; 179 of them were felt to have uncomplicated myocardial infarction. After early exercise testing, 80 patients with no provocable myocardial ischemia were randomly assigned to discharge on day 3 or discharge on day 7 to 10. Seventy-six of these patients had received coronary reperfusion therapy. The patients had at least 6 months of follow-up, and no deaths were reported in either group. Rate of hospital readmissions, reinfarctions, and angina were similar in both groups. Hospital charges were obviously significantly less in the early-discharge group. The authors call for a more largescale trial of the safety of early hospital discharge. As the era of cost containment and myocardial reperfusion merge, we may be seeing a more rapid turnover of uncomplicated myocardial infarction patients. This has obvious implications for the potential emergency department “reevaluation” visits of such patients. Thrombolytic therapy: Current status (part 1). Marder Sherry S. N Engl J Med 1988;318:1512-1520.
V,
Thromholytic therapy: Current status (part 2). Marder Sherry S. N Engl J Med 1988;318:1585-1595.
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Unresolved clinical pharmacologic questions in thromholytic therapy for acute myocardial infarction. Sherry S. J Am Co11 Cardiol 1988;12:519-525. A symposium: Silent myocardial lschemla and lnfarctionPast, present and future. Lauler D (ed). Am J Cardioll988; 61(12). Considerable literature on thrombolytic therapy and silent myocardial ischemia has been published recently. Space does not permit the review of all pertinent articles. The above review articles are a good place to start for recent events and current concepts. In regard to thrombolytic therapy, the author of the third article in this list says, “Review of the available data raises serious questions as to the validity of current views and the appropriateness of prevailing trends.”
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CRITICAL CARE TRANSPORT Feasibility and safety of emergency interhospital transport of patients during early hours of acute myocardial infarction. Gore J, Corrao J, Goldberg R, et al. Arch Intern Med 1989; 149:353-355. Identification and transport of patients with acute myocardial infarction for thromholytic therapy. Bumey R, Walsh D. Ann Emerg Med 1988;17:1158-1165. Reperfusion arrhythmia: Myth or reality? Bumey R, Walsh D, Kaplan L, et al. Ann Emerg Med 1989;18:240-243. The first article is a prospective analysis of 57 patients transported by ground or air. Before transport, 81% of patients were having chest discomfort, 23% were hypotensive, and 21% had high-grade ventricular ectopy or nonsustained ventricular tachycardia. During transport, 72% continued to have chest discomfort; however, only 4% were hypotensive. Nine percent continued to have arrhythmias, but their instability was considered noncritical. The occurrence of these complications in transport did not appear to be related to distance traveled or mode of transportation, but this was not studied rigorously. All patients survived and 93% were eventually discharged. The authors conclude that the rapid referral and transport of these patients for definitive care at their tertiary care facility has significant benefit and that the transport can be undertaken safely. They point out that it is impossible to estimate what the outcome would have been if the patients had remained at their referring hospitals, but note that current studies suggest that rapid therapeutic coronary intervention may have a significant impact on the patients’ health care. In the second and third articles, the experience at another major center is reviewed, with conclusions similar to those of the fist article. Defibrillation safety in emergency helicopter transport. Dedrick D, Darga A, Landis D, et al. Ann Emerg Med 1989; 18:69-71. Defibrillation in the close-quarter metallic environment of the helicopter has been a significant concern to transport teams. This study used a test model in the helicopter environment and found that a maximum of 1.5 mA of transient leakage occurred with a standard battery-powered defibrillator. This is well within the accepted safety standard of 50 mA. In-flight tests revealed no interference with avionics or medical equipment and adequate clearance for medical personnel. A survey of flight programs revealed that 87% of 69 programs had defibrillated in the air without hesitation or complications. Another 10% had not had to defibrillate in the aircraft. Only 2.5% of programs flew aircraft that they felt were too small to allow safe defibrillation. Pediatric critical care transport: Is a physician always needed on the team? McCloskey K, King W, Byron L. Ann Emerg Med 1989;18:247-249. This study reviewed drugs used, procedures performed, and questionnaires given to the flight crew to assess when a physician seemed necessary on a pediatric critica care transport team. In 46%, a physician was deemed to be not necessarily required for the transport’s success. The group
concludes that it may not always be necessary to send a physician as part of a critical care transport team. The problem is that despite being able to identify some flights retrospectively that did not require a physician in transport, there are no data cited that pertain to how one would prospectively identify the need for a physician. By their own data, the authors show that the environment is such that a physician would be needed >50% of the time. This would therefore mean that if a physician were not sent, the odds would be high that the physician would be needed and not available. It seems one could easily draw the conclusion that a physician should always be on the pediatric critical care transport team in view of the very high likelihood of being needed.
GASTROINTESTINAL Prophylactic sclerotherapy before the first episode of variceal hemorrhage in patients with cirrhosis. Sauerbruch T, Wotzka R, Kopcke W. N Engl J Med 1988;319:8-15. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices: A prospective multicenter study. North Italian Endoscopic Club. N Engl J Med 1988;319:983-989. The issue seems settled that sclerotherapy is the appropriate treatment for active variceal bleeding. An ancillary question has been what to do when endoscopy is undertaken and diagnoses varices that are not the active bleeding site at the time. In the first study, 133 patients at several German health centers were randomly assigned, with 68 receiving prophylactic sclerotherapy and 65 receiving no prophylaxis. The incidence of bleeding and the mortality rate during a 22month mean follow-up period was slightly lower in the prophylaxis group, but not significantly so. The authors conclude that overall, prophylactic sclerotherapy does not significantly reduce either of these phenomena. They did identify a subgroup of patients with moderately decompensated (Child class 8) alcoholic cirrhosis who may benefit from prophylactic sclerotherapy by reduction of the incidence of bleeding. In the second study, 321 patients in Italian centers were studied to identify whether clinical features and appearances of the varices could identify those at highest risk for bleeding. Patients were followed in the study for up to 38 months; during this time 85 patients had episodes of bleeding. The authors found that the prognostic index using the Child’s classification, the size of the varices, and the presence of certain markings on the varices was significantly related to the risk of bleeding. They conclude that the prognostic index can be used to identify candidates for prophylactic treatment.
GENERAL The therapeutic efficacy of critical care units: Identifying subgroups of patients who benefit. Ron A, Aronne L, Kalb P. Arch Intern Med 1989; 149:338-341. Impact of critical care physician &&lug on patients with septic shock in a university hospital medical intensive care unit. 551
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Reynolds H, Haupt M, Thill-Baharozian 1988;260:3446-3450. Outcomes in critical 1988;260:3487.
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Together these three articles further emphasize and focus on the efficacy of critical care medicine. The first report defines a subgroup of patients that had an improved outcome based on survival stratified by severity of illness and stability. The general category that showed improved outcome was the group of unstable patients with moderate illness. None of three remaining categories (stable, not ill; stable, moderately ill; and unstable, severely ill) showed significant benefit from direct critical care unit admissions. This study begins to examine a multitude of factors that may help predict at the time of admission which patients should be directly admitted to critical care units. The retrospective study of Reynolds et al compares two consecutive 1Zmonth periods: one in which faculty without specific critical care medicine training supervised a medical intensive care unit and one in which physicians with critical care medicine training supervised the same unit. Patients’ acute physiology and chronic health evaluation scores were similar during the two periods; however, the mortality was significantly lower during the critical care medicine-supervised period. The frequency of use of mechanical ventilation was not significantly different, but invasive procedures such as pulmonary artery catheters and systemic arterial catheters were used more frequently during the period in which faculty formally trained in critical care medicine supervised. The suggestion of this study is that formal training in critical care medicine can improve the survival rate of patients. In his editorial, Dr Bone comments on the need for reexamination of the reimbursement schemes for critical care medicine based on severity of illness. He also calls for more ethical, legal, and economic research into critical care medicine and recognition of “centers of technology in critical care medicine.” Patients’ and families’ preferences for medical intensive care. Danis M, Patrick D, Southerland L, et al. JAMA 1988; 260:797-802;839-840. This study used a retrospective survey technique of patients aged 255 years who had experienced previous medical intensive care unit hospitalizations in a university teaching hospital. Family members were interviewed if the patient had died during the hospital stay. Interestingly enough, 70% of patients and families were 100% willing to undergo intensive care therapy again to achieve even 1 month of survival. Only 8% were completely unwilling to undergo intensive care unit treatment again to achieve prolonged survival. The preferences for this were poorly correlated with functional status or quality of life and were not altered by life expectancies for the majority of the respondents. Similarly, age, severity of critical illness, length of stay, and charges for previous intensive care unit stays did not influence the patients’ willingness to undergo additional intensive care unit experiences. Together these data suggest that families are not negatively influenced by one previous intensive care unit experience and that realistic expectations of the future are not likely to play an important role in patient- or family552
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motivated choices for future use of limited health care resources in the intensive care unit setting.
HEMOOYNAMIC MONITORING Bedside catheterization of the pulmonary artery: Risks compared with benefits. Matthay M, Chatterjee K. Ann Intern Med 1988;109:826-834. The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. Stevenson L, Perloff J. JAMA 1989;261:884-888. Cardiac output changes and continuous mixed venous oxygen saturation measurement in the critically ill. Vaughn S, Puri V. Crit Care Med 1988;16:495-498. The pulmonary artery catheter: The debate continues. Sibbald W, Sprung C. Chest 1988;94:899-901. The first article outlines the relative risks and benefits of using pulmonary artery catheters in critically ill patients. It reviews the theoretical and practical applications of the device. Guidelines and alternatives to the pulmonary artery catheter are discussed. The study by Stevenson and Perloff prospectively examined physical signs of congestive heart failure and compared them with the hemodynamic measurements obtained from the Swan-Ganz catheter in 50 patients with known chronic heart failure. Rales, edema, and elevated mean jugular venous pressure were absent in 18 of 43 patients with markedly elevated pulmonary capillary wedge pressures. These signs of congestive heart failure had a 58% sensitivity and 100% specificity in this group. They concluded, as has been the experience of many before, that physical examinations are not reliable in chronic failure in all patients, and in many patients may result in inadequate therapy. The article by Vaughn and Puri examined 46 patients admitted to a critical care unit. They examined the efficacy of a pulmonary artery catheter that gives fiberopticmeasured continuous measurement of mixed venous O2 saturation. Patients with this catheter were nonrandomly compared with a group in which standard pulmonary artery catheters were inserted. Patients were suffering from acute myocardial infarction, cardiogenic shock, or respiratory failure or needed preoperative hemodynamic monitoring. The authors were unable to document any particular clinical value to continuous monitoring of the mixed venous 0, saturations. Further, they were unable to use the measurement as an early predictor of cardiac output changes, drawing into question the value of this expensive device. The final editorial by Sibbald and Sprung reexamined the controversy ignited by articles by Gore et al and Robin that appeared in Chest in 1987. It provides interesting reading and a lively summary of the current controversies surrounding pulmonary artery catheter use.
IATROGENESIS An attachable silver-impregnated cuff for prevention of infection with central venous catheters: A prospective randomized multicenter trial. Maki D, Cobb L, Garman J, et al. Am J Med 1988;85:307-314.
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A novel silver-impregnated attachable cuff was used to reduce signticantly the catheter-related infections from percutaneously inserted central venous lines. Patients were randomly assigned to central venous lines with or without the silver-impregnated cti. A significant reduction in catheter colonization (28.9% v 9.1%) and bacteremia (3.7% v 1.O%) occurred with the use of this cuff. Prospective study of catheter-related infection during prolonged arterial catheterization. Norwood S, Cormier B, McMahon N, et al. Crit Care Med 1988;16:836-839. Fifty-six surgical intensive care unit patients were prospectively studied using 96 arterial catheters from 75 different anatomical sites. Every 96 hours, all catheters were semiquantitatively cultured and the entry sites were swabbed and cultured. It was concluded that arterial catheter-related infections develop in < 10% of radial and femoral sites, even when these catheters are used for >96 hours. The majority of radial and femoral arterial sites (90%) remained clear for long periods, particularly when the percutaneous colonization sites were controlled. This study also suggests that skin site swab cultures may be useful in determining when arterial catheters should be removed and semiquantitatively cultured. Prevention of colonization and infection in critically ill patients: A prospective randomized study. Kerver A, Rommes J, Mevissen-Verhage E, et al. Crit Care Med 1988;16:10871093. Effects of gastric alkalization on bacterial colonization in critically ill patients. Garvey B, McCambley J, Tuxen D. Crit Care Med 1988;17:211-216. These two clinical investigations provide increasing evidence that gram-negative bacteria counts are altered in critically ill patients. In the study by Kerver et al, attempts were directed at reducing the bacterial load of critically ill patients by treating a randomized group with nonabsorbable antimicrobial agents including tobramycin, amphotericin B, and polymyxin E. In addition, these patients received parenteral cefotaxim for five to seven days. Compared with the nontreated control group, significantly fewer episodes of nosocomial infections and resulting mortality occurred. In the study by Garvey et al, the effect of gastric alkalization on critically ill patients was examined. All 25 patients received antacids every 12 hours, and 15 of 25 received additional HZ-receptor antagonists. They then underwent nasogastric, urine, and tracheal secretion culturing on a regular basis. Many were receiving systemic antibiotic therapy. It was demonstrated that colonization occurs despite concurrent appropriate antibiotics, and that this colonization is universal in alkalinized gastric solutions. This study was limited in its scope because no control group was monitored without gastric alkalinization therapy to determine whether this process is simply secondary to the effect of alkalinization of the gastric secretions or to the degree of illness.
INFECTIOUS DISEASE Treatment of gram-negative septic shock with human IgG antibody to Escheriehio coli J5: A prospective, double-blind,
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randomized trial. Calandra T, Glauser M, Schellekens J, et al. J Infect Dis 1988;158:312-319. Phase I study of a murine monoclonal anti-lipid A antibody in bacteremic and nonhacteremic patients. Harkonen S, Scannon P, Mischak R, et al. Antimicrob Agents Chemother 1988;32:710-716. There has been a burgeoning effort to find an antidote to gram-negative endotoxin via use of antibody to the J5 antigen. This Escherichia coli antigen is felt to be shared by many gram-negative endotoxin molecules. The fust article studied 100 patients, 71 of whom had documented gramnegative infections. A human immunoglobulin against J5 antigen was compared with a standard pooled immunoglobulin preparation. This study found that there was no difference in the number of systemic complications of shock and no difference in mortality. The second studied a similar but murine monoclonal antibody in nine patients. This preliminary study demonstrated that the preparation appeared to be well tolerated. At the higher dosage range, however, the murine antibody may well be immunogenic. Large-scale controlled trials of both human and murine monoclonal antibodies are underway at present. It is hoped that these large-scale trials will demonstrate a therapeutic benefit to the use of this compound. Dexamethasone therapy for bacterial meningitis: Results of two double-blind, placebo-controlled trials. Lebel M, Freij B, Syrogiannopoulos G, et al. N Engl J Med 1988;319:964971. This article reports the combined results of two prospective placebo-controlled trials using dexamethasone therapy in infants and older children with bacterial meningitis. The study found similar mortality rates but more rapid reversal of CSF values in the dexamethasone-treated group. The significant differences between the groups was that the dexamethasone-treated group became afebrile earlier and had a lower incidence of sensorineural hearing loss. On the basis of these data, the authors conclude that dexamethasone should be routinely administered during the first four days of antimicrobial therapy in infants and children. Acyclovir-resistant herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. Erlich K, Mills J, Chatis P, et al. N Engl J Med 1988;320:293-2%. Resistance to antiviral drugs: The end of innocence. Hirsch M, Schooley R. N Engl J Med 1988;320:313-314. The titles of this report and the accompanying editorial are almost self-explanatory. The report describes 12 patients with acquired immunodeficiency syndrome (AIDS) over a 2!&year period who developed acyclovir-resistant herpes infections. The likely setting for ongoing problems with acyclovir-resistance is the AIDS population. However, unjudicious use of acyclovir will presumably result in increasing frequency of resistance to antiviral drugs. We must therefore concern ourselves with judicious use of such agents in the hopes of prolonging the point when we see multiply resistant viruses just as we see many highly resistant bacteria in the modern era. 553
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NEUROLOGICAL Leftventricular wall motion abnormalities in subarachnoid hemorrhage: An echocardlographic study. Pollick C, Cujec B, Parker S, et al. J Am Co11 Cardiol 1988;12:600-605. Increased intracranial pressure elicits hypertension, increased sympathetic activity, electrocardiographic abnormalities and myocardial damage in rats. Shanlin R, Sole M, Rahimifar M, et al. J Am Co11 Cardiol 1988;12:727-736. These studies represent further data confirming that neurological lesions can produce cardiac abnormalities. The first study reports on 13 patients, four of whom exhibited left ventricular wall motion abnormalities despite no history of heart disease. Their neurological grades were significantly worse than those without wall motion abnormalities, and all four had T-wave inversions (v one of nine without wall motion abnormalities). These cardiac abnormalities associated with high-neurological-grade subarachnoid hemorrhage are readily detected by the two-dimensional echocardiographic techniques used in this study. The second article reports on 59 rats with experimental intracranial hypertension. The rats were found to have significant increases in plasma catecholamines and areas of focal constriction with microvascular spasm on myocardial histological examination. These observations suggest that myocardial damage and abnormalities noted in intracranial hypertension may result from both of these phenomena. The data are significant in terms of both the management of victims of intracranial hypertension and the implications for organ transplant. Does magnesium sulfate treat eclarnptic seizures? Yes. Dinsdale H. Arch Neurol 1988;45: 1360-1361. No, magnesium sulfate should not be used in treating eclamptic seizures. Kaplan P, Lesser R, Fisher R, et al. Arch Neurol 1988;45:1361-1364. These two articles highlight the controversy over a longaccepted obstetric practice. The authors of the second article argue that standard antiseizure medicines are much better therapy for eclamptic seizures than magnesium. Although they admit that magnesium therapy may have a role in the treatment of preeclampsia, they argue that the risks of magnesium and of standard anticonvulsants are equivalent, whereas magnesium is not as effective an anticonvulsant, or even a proven one.
PHARMACOLOGY Attenuation of acute lung injury in septic guinea pigs by pentoxifylline. Ishizaka A, Wu Z, Stephens K, et al. Am Rev Respir Dis 1988;138:376-382. Pentoxlfylline improves survival following hemorrhagic shock. Coccia M, Waxman K, Soliman H, et al. Crit Care Med1989;17:36-38. Pentoxifylhne decreases endotoxin-induced pulmonary neutrophil sequestration and extravascular protein accumulation in the dog. Welsh C, Lien D, Worthen S, et al. Am Rev Respir Dis 1988;138:1106-1114. 554
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ARDS, neutrophlls, and pentoxifylllne. Mandell G. Am Rev Respir Dis 1988;138: 1103-l 104. Pentoxifylline is a drug approved for use in claudication and other peripheral vascular circulation problems. It is a methylxanthine that increases intracellular cyclic AMP. These three studies demonstrate a marked reduction in lung injury with pentoxifylline in models of shock. The first study used E coli injected in guinea pigs with constant pentoxifylline infusion before exposure. Similarly, in the third study pentoxifylline was demonstrated to decrease neutrophil pulmonary accumulation and prevent increases in pulmonary vascular permeability to proteins induced by salmonella endotoxin in dogs. When pentoxifylline was added to ringers solution in the resuscitation of rats after hemorrhagic shock, significant improvement in survival was demonstrated. The final editorial discusses possible mechanisms of pentoxifylline action in these shock conditions. The possibility that pentoxifylline interacts with the inflammatory cytokines, either by decreasing production of tumor necrosis factor and interleukin-1 or by stabilizing phagocytes and other cells, is cited. Together, these data suggest that pentoxifylline or derivatives of pentoxifylline may be important in the shock resuscitation of the future. The effects of midazolam reversal by RO 15-1788 on cerebral perfusion pressure in patients with severe head injury. Chiolero R, Ravussin P, Anderes J. Intensive Care Med 1988; 14: 196-200. The benzodiazepine antagonist RO 15 1788 (flumazenil) is currently being evaluated for potential use in the United States. This study examines the effects of reversing midazolam sedation in 15 patients with severe head injuries (Glasgow coma scale ~8). Those patients who had poor control of intracranial pressure (ICP) before receiving the benzodiazepine antagonist had a significant increase in ICP after reversal of the midazolam. Those patients with good control of ICP before treatment with the benzodiazepine antagonist had no significant change in ICP. Arousal after midazolam reversal was obvious in five patients, who were then quickly extubated. This study suggests that while the benzodiazepine antagonist may well have an important role in headinjured patients, great care must be exercised because it can exacerbate elevated or poorly controlled ICP. Propylene glycol-induced side effects during intravenous nitroglycerin therapy. Denney H, Daelemans R, Verpooten G, et al. Intensive Care Med 1988;14:221-226. This important study reviews 28 consecutive patients who received intravenous nitroglycerin for acute myocardial infarctions or preload reduction. The intravenous doses and durations of therapies ranged from 0.5 to 6 &kg per minute of nitroglycerine for 1 to 12 days. Propylene glycol is used as a solvent for a large number of drugs including some intravenous nitroglycerine preparations. In this study, 10.5% of the patients had evidence of acute hemolysis. Hemoglobinuria was present in 3.5% of the cases. Serum osmohdity increased by 54 mosmlkg with the nitroglycerine infusion. Together these data suggest that subtle toxicity from propylene glycol may be a contributing factor to the morbidity
FOULKE AND ALBERTSON H CRITICAL CARE MEDICINE: ANNOTATED BIBLIOGRAPHY
associated with certain nitroglycerine infusion preparations and other drugs that use propylene glycol diluent.
PROCEDURES AND TECHNIQUES
evidence cited in this study suggests that this technique can be used to inactivate endotoxin in the blood with polymyxin B.
RESPIRATORY
Intraosseous infusion of muscle relaxants. Katan B , Olshaker J, Dickerson S. Am J Emerg Med 1988;6:353-354.
An expanded definition of the adult respiratory distress syn-
The authors successfully used an intraosseous line for infusion of succinylcholine chloride, atracurium besylate, and thiopental. This is the first report of such a technique. Although it is a single case report of use in a 6?&month-old, 7.5kg child, it highlights the potential for use of this technique in administering a wider range of emergent drugs in the pediatric age group.
Diagnostic criteria for adult respiratory distress syndrome time for reappraisal. Rocker G, Pearson D, Wiseman M, et al. Lancet 1989;1:120-123.
Emergency flexible fiberoptic nasotracheal intubation: A report of 60 cases. Delaney K, Hessler R. Ann Emerg Med 1988; 17:919-926. Use of flexible fiberoptic endoscopy for determination of endotracheal tube position in the pediatric patient. Dietrich K, Strauss R, Cabalka A, et al. Crit Care Med 1988;16:884887. The first article reports a series of 60 patients in which emergency flexible fiberoptic nasotracheal intubation failed in only 13%. There was a 22% incidence of bleeding and a 9% incidence of esophageal intubation. Overall the report highlights at least one center’s successful use of the technique for difficult intubations. In high-acuity (particularly trauma) centers, the technique should probably become more widely used. The second article documents the utility of the fiberoptic technique for determining proper endotracheal tube placement. The only difference between this technique and the use of a chest radiograph for tube placement was time differential (mean, 40 seconds v 30.6 minutes, respectively). The only complicating feature is the presence of copious secretions. Otherwise this is a rapid, highly reliable, safe, and highly useful technique. Placement of multiorlficed CVP catheters via antecubital veins using intravascular electrocardiography. Artru A, Colley P. Anesthesiology 1988;69:132-135.
drome. Murray J, Matthay M, Lute Respir Dis 1988;138:720-723.
J, et al. Am Rev
These two articles offer extensive refinement to the evaluation and definition of the adult respiratory distress syndrome (ARDS). The paper by Murray et al defines a useful lung injury score for evaluating the degree of pulmonary damage in ARDS patients. In addition, a table outlining the characteristics of parenchymal lung injury and further detining this heterogenous group of patients is provided. Rocker et al provide additional diagnostic criteria for ARDS patients. They specifically have examined the continuum of ARDS patients with regards to their hypoxia, plasma elastase complex, and bronchoalveolar iavage protein content. This analysis points out that the condition recognized as ARDS is not a distinct pathophysiological entity but a continuum of lung injury. The prone position in ARDS patients: A clinical study. Langer M, Mascheroni D, Marcolin R, et al. Chest 1988;94:103107. This article examines body position in the ARDS patient. More than 50% of the patients in this study improved their Pao, by at least 10 mmHg after 30 minutes in the prone position. When one of the “responder” patients were compared with a “nonresponder” patient by computerized tomography in the prone and supine positions, posterior basal densities disappeared with appearance of new anterior region densities in both patients. The etiology of the improvement in blood gases was not obvious from this study; however, the realization that ARDS affects the lung tissue in a nonhomogenous manner is certainly brought out. Cold-induced pulmonary oedema in scuba divers and swimmers and subsequent development of hypertension. Wilmshurst P, Nuri M, Crowther A, et al. Lancet 1989;1:62-65.
A past report by these authors regarding the use of a catheter guided by intravascular ECG delineated less than satisfactory success rates and insertion times. The new report contained in this article reveals more satisfactory results with this rather innovative technique. In a very controlled anesthesia setting, the catheter was successfully placed in 58 of 60 patients with a mean time of 6.3 ? 3.6 minutes. This required a total of 91 attempts. This unusual technique might be considered in certain patients (bums, etc) in whom vascular access is difficult in the usual central venous locations.
This article offers an additional etiology of ARDS. The effects of cold water or increased partial pressure of oxygen were examined in 11 divers with a history of pulmonary edema while at-depth or surface swimming. Evidence of cold-induced pulmonary edema and cardiac decompensation was seen in some of these patients. The exact mechanism for this cold-induced pathophysiology is unknown at this time.
New approach to endotoxic and septic shock by means of polymyxin B immobilized fiber. Hanasawa K, Tani T, Kodama M. Surg Gynecol Obstet 1989;168:323-331.
Protection against pulmonary 0, toxicity by N-acetylcysteine. Wagner P, Mathieu-Costello 0, Bebout D, et al. Eur Respir J 1989;2:116-126.
This fascinating study in 12 dogs shows successful treatment of endotoxic shock using hemoperfusion over a fiberous carrier impregnated with polymyxin B. The preliminary
This study of 12 anesthetized dogs exposed to prolonged 100% oxygen demonstrated that N-acetylcysteine, a known antioxidant, protected against oxygen-caused functional and
AMERICANJOURNAL OF EMERGENCYMEDICINEn Volume 7, Number 5 n September 1989
structural abnormalities. This study is a prodrome to current clinical studies examining the effectiveness of Nacetylcysteine in ARDS and other lung conditions thought to result from toxic free radicals. Effect of verapamil on pulmonary and eicosanoid responses to endotoxin in awake sheep. Ahmed T, D’brot J, Wasserman M, et al. J Appl Physiol 1988;64:1700-1708. Using the sheep model with E cofi endotoxin, this study demonstrated that pretreatment with verapamil, 150 &kg, followed by continuous infusion of verapamil after endotoxin exposure, blunted the normal increase in lung resistance and decrease in Pao,. At this dose, verapamil pretreatment did not alter endotoxin-induced changes in pulmonary vascular resistance, WBC counts, arterial thromboxane B,, prostaglandin F2_, or 6-ketoprostaglandin F,, concentrations. At higher doses, verapamil demonstrated substantial blunting and attenuation of endotoxin-induced changes in pulmonary hemodynamics, airway mechanics, leukocyte count, and cyclooxygenase metabolites. It may have an important potential therapeutic role in endotoxin-induced lesions. Future clinical trials are needed. Role of brain lactic acidosis in hypoxic depression of respiration. Neubauer J, Simone A, Edelman N. J Appl Physiol 1988;65:1324-1331. This study with anesthetized, paralyzed cats showed that ventral medullary acidosis resulted in greater depression of phrenic nerve activity for any given level of brain hypoxia. Lactic acidosis near the central chemosensitive regions of the midbrain can produce a small stimulation of respirations during progressive brain hypoxia, but the overwhelming response to central lactic acidosis of progressive brain hypoxia is respiratory depression. This pathophysiological finding points to lactic acidosis as a contributing factor to the downhill spiral associated with progressive brain hypoxia.
SHOCK AND RESUSCITATION Hemorrhagic shock induces bacterial translocation from the gut. Baker J, Deitch E, Berg R, et al. J Trauma 1988;28: 8%~903. Endotoxemia and bacteremia during hemorrhagic shock. Rush B, Sot-i A, Murphy T, et al. Ann Surg 1988;207:549-554. Considerable attention has recently been focused on the gastrointestinal tract and the breakdown of normal barriers to bacterial translocation. The first article reports on bacterial translocation to mesenteric lymph nodes, livers, and spleens of rats subjected to hemorrhagic shock. There was a significant correlation between this event and the amount of time of shock. There was no correlation in a sham-operated group. The second article reports on a similar model in 26 rats, with findings of bacteremia and endotoxemia in 50% and 87%, respectively. Also reported are some preliminary findings regarding these same events in severe trauma patients. Although flawed in certain ways, both of these studies suggest a phenomenon that those of us practicing critical care medicine have long suspected. 556
Detection of circulating tumor necrosis factor after endotoxin administration. Michie H, Manogue K, Spriggs D, et al. N Engl J Med 1988;318:1481-1486. Much work has been done on the substance known as tumor necrosis factor and its relationship to the chain of events whereby endotoxin might produce injury and septic shock. This rather adventuresome study looked at levels of tumor necrosis factor (cachectin), interleukin-lB, and gamma interferon in 13 healthy volunteers who were administered E co/i endotoxin. Control levels of cachectin were ~35 pg/mL but increased 90 to 100 minutes after endotoxin to mean peak levels of 240 * 70 pg/mL. Interleukin-l@ and gamma interferon levels did not change. The authors cite these data as evidence that the response to endotoxin is associated with a pulse of cachectin and that the resultant downstream responses are effected through the cyclooxygenase pathway. Human recombinant tumor necrosis factor alpha infusion mimics endotoxemia in awake sheep. Johnson J, Meyrick B, Jesmok G, et al. J Appl Physiol 1989;66:1448-1454. The findings in this study complement the data in the article above. Using the sheep lung lymph tistula model, the authors studied the effect of infusion of tumor necrosis factor on subsequent physiology. Pulmonary artery hypertension, hypoxemia, and peripheral blood and lung lymph leukopenia all occurred during the four hours of the study. These were followed by increases in protein-rich lung lymph flow consistent with an increased microvascular permeability in the pulmonary bed. These changes are all very similar to the changes seen in this model with endotoxin infusion. The authors conclude that tumor necrosis factor induces a response remarkably similar to that of endotoxemia and that it may mediate endotoxin-induced lung injury. Role of endotoxemia in cardiovascular dysfunction and mortality. Natanson C, Danner R, Elin R, et al. J Clin Invest 1989;83:243-251. This is another in a series of studies by the group that has done the most work characterizing cardiovascular dysfunction in sepsis. In this animal study there were 14 control dogs and 74 infected dogs. This study used E coli and Staphylococcus aureus as the bacterial agents. It further characterizes the myocardial depression and cardiovascular changes associated with E coli infection and endotoxemia. Interestingly enough, the S aureus-infected dogs who did not demonstrate any endotoxemia had similar cardiovascular changes. The authors cite these data as evidence that markedly different organisms with and without endotoxin production can incite some common pathway, resulting in the cardiovascular changes seen in sepsis.
VENTILATION Best PEEP: Issues and choices in the selection and monitoring of PEEP levels. Kirby R. Respir Care 1988;33:569-576. Positive end-expiratory pressure: Reduction and withdrawal. Hudson L, Weaver J, Haisch C, et al. Respir Care 1988; 33:613-617.
FOULKE AND ALBERTSON
The first article (from an issue completely devoted to a symposium on the topic) reviews past and recent studies on how to find the “best” level of positive end-expiratory pressure (PEEP). It seems we have come full circle on this topic. In past years, studies of very high levels of PEEP were published. Some recent studies suggest that the lowest level of PEEP which achieves adequate oxygenation with an FIo, ~50% may be best in both the acute and chronic phases. The second article discusses an interesting subject on which a minimal amount of data are available. Based on the past studies cited and their own work contained in the article, the authors recommend reduction of PEEP by 5 cm H,O at a time with an interval of less than every six hours. They also recommend reduction for a three-minute period and then return to a baseline level while a blood gas analysis is obtained (a so-called three-minute PEEP trial). Their data suggest that patients who go through this short interval of PEEP reduction successfully are likely to be candidates for continued PEEP reduction. Pressure controlled inverse ratio ventilation in severe adult respiratory failure. Tharratt R, Allen R, Albertson T. Chest 1988;94:755-762.
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Clinical trials of some of the more recent ventilatory modalities are now making their way into the literature. This article reports a series of 31 patients receiving inverse-ratio ventilation. Peak inspiratory pressure was reduced from 66 + 2.3 to 48 f 1.6 cm H,O. PEEP was reduced from 15 & 1.0 to 2.5 -+ 0.5 cm H,O. Oxygenation was improved. The authors conclude that inverse-ratio ventilation can be successfully and safely implemented in critically ill patients in a manner such that it provides improved oxygenation at lower minute volume, peak airway pressure, and PEEP requirements. Airway pressure release ventilation (APRV): A human trial. Garner W, Downs J, Stock M, et al. Chest 1988;94:779781. This is an initial report of a human trial of the airway pressure release ventilation (APRV) modality. Fourteen patients undergoing elective coronary operations received conventional ventilation and then were studied with APRV in the postoperative period. The authors conclude that APRV supported oxygenation and ventilation in patients with mild lung injury at much lower peak airway pressures than produced by conventional ventilation.
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