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Biomedical subjects

N A Halpern

Publications and source records attributed to N A Halpern.

At least 19 recordsLinked to original sources
PubMed2005

A safety evaluation of drotrecogin alfa (activated) in hematopoietic stem cell transplant patients with severe sepsis: lessons in clinical research.

We conducted an open-label, multicenter, single-arm clinical trial to investigate the safety and efficacy of drotrecogin alfa (activated) (Drot AA) in hematopoietic stem cell transplant (HSCT) patients with severe sepsis. Drot AA was administered as a continuous i.v. infusion of 24 microg/kg/h for 96 h. The target enrollment was 250 patients in 15-20 transplant centers over a 2-year period (March 2003-March 2005). However, after only 10 months, in December 2003, the trial was stopped due to a low enrollment of seven patients at three of the 15 sites that were open for accrual. Six of the seven patients completed the drug infusion. Two patients experienced serious bleeding events. The first patient developed a nonfatal diffuse alveolar hemorrhage 2 days after study-drug completion. The second patient had severe coagulopathy and developed a fatal intracranial hemorrhage on the third day of drug infusion. Three of the seven patients were alive 100 days after the HSCT. The slow enrollment rate was attributed to changes in transplant preparatory regimens, enhancements in antimicrobial prophylactic protocols and the use of antimicrobial-coated catheters. The small number of patients in this report precludes a definitive assessment of the safety and efficacy of Drot AA in HSCT patients.

Adult↗
PubMed2002

Septic shock and multiple organ failure after hematopoietic stem cell transplantation: treatment with recombinant human activated protein C.

Severe sepsis with multiple organ failure after hematopoietic stem cell transplantation (HSCT) results in extremely high morbidity and mortality. Recent studies have highlighted the importance of sepsis-induced activation of the coagulation system in the pathophysiology of severe sepsis. Activated protein C is an important modulator of coagulation and inflammatory derangements during severe sepsis. Low levels of protein C occur in severe sepsis and are predictive of poor outcome. Recombinant human activated protein C (drotrecogin alfa (activated)) was recently approved by the Food and Drug Administration (FDA) for severe sepsis. The phase III trial that resulted in the approval of this agent, however, enrolled a general sepsis population and excluded patients undergoing HSCT. We report a case of fulminant septic shock and multiple organ failure after HSCT that was treated with drotrecogin alfa (activated) in addition to standard therapy, and recovered. The high mortality rates of patients who develop severe sepsis after HSCT demand that new avenues of treatment be considered for this very high-risk patient population. This case illustrates the potential application of a novel therapeutic approach. Clinical trials are warranted to further investigate the safety and efficacy of drotrecogin alfa (activated) in patients with severe sepsis after HSCT.

Adult↗
PubMed2000

Acquisition strategies for critical care technology.

Technological advances in critical care will undoubtedly find their way into the ICU of the 21st century. The challenge for critical care practitioners is to meticulously assess these innovations and adopt the most appropriate and efficient technologies that will improve unit function and staff efficiencies, support educational programs, and most importantly, enhance patient outcome at a reasonable cost. Hospital-based intensivists have excellent opportunities to establish leadership roles in the technology evaluation process by cultivating relationships with administrators, and through active participation in the hospital-based Technology Committee and the ICU-based multidisciplinary committee. The authors' experience has left them with the lasting impression that the evaluation and introduction of new technology is time consuming and requires perseverance and patience. Ultimately, it is hoped that technological breakthroughs coupled with a standardized approach to delivery of ICU services in the coming decades will ensure better and more efficient care to critically ill patients.

Cost-Benefit Analysis↗
PubMed2000

Point of care diagnostics and networks.

The new paradigm of POCT as integrated into the ICU will allow for an improved and more efficient critical care workplace and possibly improvements in outcome and costs. Technologic advances in POCT will focus on enhancements of current devices, connectivity, and data management and on the introduction of novel diagnostic and therapeutic approaches. It is hoped that in the future the regulatory, laboratory, and L/HIS communities will recognize the need to accept, integrate, accommodate, and expand POCT, thereby promoting bedside diagnostics. For ongoing follow-up of the myriad of POCT projects, refer to the POCT websites listed in Table 1.

Clinical Laboratory Information Systems↗
PubMed2000

Bioartificial organ support for hepatic, renal, and hematologic failure.

The current strategy to the treatment of SIRS and MODS uses a multidisciplinary approach that emphasizes supportive therapy. Herein, we have presented a futuristic approach that focuses on replacing the function of failed organs using bioartificial technology (Table 1). Bioartificial organ technology may allow the intensivist to provide physiologic organ replacement either as a bridge to transplantation or as a "time-buying" element until native organs that have become acutely dysfunctional or nonfunctional in a variety of clinical settings, can recover their function or regenerate their mass. As bioartificial organ technology matures, it is conceivable as an ultimate goal that non-immunogenic bioartificial organs would be miniaturized or redesigned and acutely placed within the intracorporeal space as replacement organs.

Bioartificial Organs↗
PubMed1999

Point of care testing informatics. The critical care-hospital interface.

Point of care testing (POCT), a new paradigm in laboratory testing, has recently been introduced to the critical care setting. In this model, laboratory testing is performed in the critical care vicinity by local bedside personnel. POCT devices perform user selected critical care tests on whole blood in a timely and accurate fashion. The POCT data, while used immediately at the bedside, must still be managed in accordance with regulatory guidelines and incorporated into the laboratory or hospital information system. Currently, critical care physicians are not educated and trained in the intricacies of laboratory data management and device interfacing. This article addresses the technical, political, and implementation issues surrounding POCT data management and interfacing as well as the philosophical and practical differences in laboratory data management between the central laboratory and POCT sites.

Clinical Laboratory Information Systems↗
PubMed1999

Hearing loss in critical care: an unappreciated phenomenon.

OBJECTIVES: The objectives of this article are to review the physiology of hearing; identify acute pathologic and perceived causes of hearing loss in the adult critically ill patient; and to discuss its evaluation, treatment, and prevention. DATA SOURCES: Computerized bibliographic search of MEDLINE from 1966 to the present of all relevant articles in all languages on acute hearing loss in the adult population. DATA EXTRACTION: Data gathered from studies and reports of acute hearing loss as relates or potentially relates to the peri-intensive care unit (ICU) period. DATA SYNTHESIS: Hearing loss is an infrequent but potentially serious complication associated with critical illness. The causes of hearing loss in the ICU patient include mechanical or accidental trauma, administration of ototoxic medications, local or systemic infections, vascular and hematologic disorders, autoimmune diseases, and environmental noise. Patients who are elderly, have coexisting liver or renal failure, or who are receiving concomitantly administered ototoxic drugs are particularly at risk for developing hearing loss. A thorough assessment of potential causes of hearing loss and audiological examination should be undertaken on all ICU patients suspected of hearing loss. Mechanical, pharmacologic, and environmental strategies are available to decrease the incidence of hearing loss in this patient population. CONCLUSIONS: Hearing loss should be recognized as a potential clinical problem by intensivists. Its causes should be identified and appropriate evaluation and therapy initiated. High risk populations should be identified for preventive measures.

Critical Care↗
PubMed1999

Carboxyhemoglobin and lactate levels do not correlate in critically ill patients.

Endogenous carbon monoxide (CO) is produced in the degradation of heme by heme oxygenase. Studies have shown that hypoxia induces heme oxygenase production of CO in vascular tissue. Because elevated plasma lactate levels are associated with tissue hypoxia, we determined if there was any correlation between lactate and carboxyhemoglobin (COHb) levels in a group of critically ill patients with a high likelihood of hypoxia. In a 7.5-month period, 5322 simultaneous arterial COHb and lactate measurements were performed routinely on 183 patients with a blood gas analyzer in the Department of Veterans Affairs Medical Center, Bronx, New York, Surgical Intensive Care Unit. Sixty-one percent of the patients had elevated lactate levels (> 2.5mmol/L), and 46% had elevated COHb levels (> 1.5%). Lactate levels ranged from 0.12 to 22.7 mmol/L and COHb levels from 0% to 4.8%. There was no correlation between lactate and COHb levels (r = .07 with P < .0001). Levels of endogenous CO do not increase in situations in which lactate production is increased. It is possible that changes in endogenous production of CO may not significantly affect the circulating level of COHb. Although readily available, COHb levels do not seem to be clinically useful as markers of critical illness.

Animals↗
PubMed1997

Isolyte S, a physiologic multielectrolyte solution, is preferable to normal saline to wash cell saver salvaged blood: conclusions from a prospective, randomized study in a canine model.

OBJECTIVES: The purpose of this study is to compare normal saline with Isolyte S as the wash solutions during high-volume cell saver autologous blood transfusion. Normal saline, the standard wash solution in cell saver autologous blood transfusion, is associated with acid-base and electrolyte derangements. Isolyte S is a physiologic, balanced multielectrolyte crystalloid solution that approximates the electrolyte content of plasma. DESIGN: Open-label, prospective, randomized study. SETTING: Research laboratory in a Department of Veterans Affairs medical center. SUBJECTS: Fourteen mongrel dogs, weighing 22 to 23 kg each. INTERVENTIONS: Fourteen mongrel dogs were prospectively randomized to receive normal saline (n = 7) or Isolyte S (n = 7). Animals were anesthetized, received heparin for anticoagulation, and underwent 18 cycles of cell saver autotransfusion. In each cycle, 125 mL of blood was arterially withdrawn, and washed with either normal saline (mEq/L) (sodium 154, chloride 154) or Isolyte S (mEq/L) (sodium 141, potassium 5, magnesium 3, chloride 98, phosphate 1, acetate 28, and gluconate 23). The washed blood was retransfused. MEASUREMENTS AND MAIN RESULTS: Acid-base and electrolyte analyses were performed throughout the study on the systemic blood of each group and compared. By the end of the study, the Isolyte S group had a normal pH and an increased bicarbonate concentration (mEq/L: normal values 24 to 32; normal saline 9.0 +/- 1.9 vs. Isolyte S 13.2 +/- 3.0 [p < .01]) and an increased magnesium concentration (mg/dL: normal values 1.6 to 2.4; normal saline 1.6 +/- 0.2 vs. Isolyte S 2.2 +/- 0.2 [p < .0001]). Additionally, the Isolyte S group had a lower chloride concentration (mEq/L: normal values 95 to 110; normal saline 130 +/- 9 vs. Isolyte S 117 +/- 7 [p < .02]) and a lower potassium concentration (mEq/L: normal values 3.5 to 5.0; normal saline 4.4 +/- 0.5 vs. Isolyte S 3.7 +/- 0.3 [p < .01]). There were no significant differences between normal saline or Isolyte S in the values of PCO2, lactic acid, sodium, total and ionized calcium, inorganic phosphorus, total protein, albumin, hemoglobin, and hematocrit. CONCLUSIONS: Fewer systemic acid-base and electrolyte derangements were observed when blood was washed with Isolyte S. Differences between the normal saline and Isolyte S groups are ascribed primarily to the constituents of the wash solution. We conclude that Isolyte S, a physiologic, balanced, multielectrolyte solution, should be considered as the wash solution in high-volume autologous cell saver blood processing and transfusion.

Animals↗
PubMed1996

Cell saver autologous transfusion: metabolic consequences of washing blood with normal saline.

OBJECTIVE: To evaluate acid-base and electrolyte changes in high volume cell saver autologous blood transfusion when normal saline (0.9% NaCl) is used as the wash solution. DESIGN: Open-label study. MATERIALS AND METHODS: Nine anesthetized and anticoagulated mongrel dogs underwent 15 cycles of cell saver autologous blood transfusion. Eight percent of the circulating blood volume (125 mL) was withdrawn, washed with normal saline, and retransfused for each cycle. MEASUREMENTS AND MAIN RESULTS: Analyses of acid-base, electrolyte, and hematologic parameters were performed on both systemic and the washed blood. The washed blood had increased levels of sodium and chloride. There were decreased levels in pH, Pco2, total CO2 (bicarbonate), lactic acid, potassium, total and ionized calcium, magnesium, inorganic phosphorus, total protein, and albumin. Systemically, in the animals, by the end of the study, there were significant increases in the levels of chloride, inorganic phosphorus, hemoglobin, and hematocrit and significant decreases in the levels of pH, total CO2, total and ionized calcium, magnesium, total protein, and albumin. CONCLUSIONS: Acid-base, electrolyte, and hematologic changes occur when normal saline is used as the wash solution in high volume cell saver autologous blood transfusion. The washed blood with its elevation of sodium and chloride appears to reflect the constituents of the wash solution, normal saline. The depletion in the washed blood of PCO2, total CO2, potassium, total calcium, ionized calcium, magnesium, phosphorus, total protein, and albumin we feel is because of the absence of these electrolytes in the wash solution and their physical removal during salvaged blood separation and washing. The systemic acid-base and electrolyte changes primarily reflect the electrolyte pattern of the reinfused washed blood except for inorganic phosphorus. Inorganic phosphorus was maintained systemically, despite its wash out in the cell salvage process. This paradoxical finding may be caused by intracellular to extracellular inorganic phosphorus flux caused by the progressive systemic metabolic acidosis.

Acid-Base Equilibrium↗
PubMed1996

A prospective randomized study of inpatient iv. antibiotics for community-acquired pneumonia. The optimal duration of therapy.

STUDY OBJECTIVE: To compare therapeutic outcome and perform a cost-benefit analysis of inpatients with community-acquired pneumonia (CAP) treated with a shortened course of i.v. antibiotic therapy. DESIGN: A prospective, randomized, parallel group study with a follow-up period of 28 days. SETTING: Bronx Veterans Affairs Medical Center (VAMC) and the Castle Point VAMC; university-affiliated VAMC general medical wards from September 1993 to March 1995. PATIENTS: Seventy-two male veterans and 1 female veteran with 75 episodes of CAP defined by a new infiltrate on chest radiograph and either history or physical findings consistent with pneumonia. Study population was 42%(31) black, 33%(24) white, and 25%(18) Hispanic. INTERVENTIONS: Patients were randomized (1:1:1) to 1 of 3 treatment groups: group 1 received 2 days of i.v. and 8 days of oral therapy; group 2 received 5 days of i.v. and 5 days of oral therapy; and group 3 received 10 days of i.v. therapy. Antibiotics consisted of cefuroxime, 750 mg every 8 h for the i.v. course, and cefuroxime axetil, 500 mg every 12 h for the oral therapy. MEASUREMENTS AND RESULTS: No differences were found in the clinical course, cure rates, or resolution of chest radiograph abnormalities among the three groups. A significant difference was found in the length of stay (LOS) among the three groups. The mean +/- SD LOS was 6 +/- 3 days in group 1, 8 +/- 2 days in group 2, and 11 +/- 1 days in group 3. The shortened LOS could potentially save $95.5 million for the Department of Veterans Affairs and $2.9 billion for the US private sector. CONCLUSIONS: Adult patients hospitalized for CAP who are not severely ill can be successfully treated with an abbreviated (2-day) course of i.v. antibiotics and then switched to oral therapy. A longer course of i.v. therapy prolongs hospital stay and cost, without improving the therapeutic cure rate.

Adult↗
PubMed1996

Acute hypertension and calcium-channel blockers.

Acute arteriolar vasoconstriction is considered to be the common physiologic pathway for hypertensive crises. Calcium plays a critical role in this process as a required element in the generation of vascular smooth muscle contraction. Within the vascular smooth muscle cell, calcium homeostasis is maintained through a complex set of mechanisms that control cellular calcium influx and efflux as well as intracellular calcium storage. Extracellular calcium enters the intracellular free space of the vascular smooth muscle cell through four portals: a passive slow leak, voltage-gated channels, hormone-mediated receptor-operated channels, and stretch-activated channels. The myofilaments actin and myosin contract upon the increase in cytosolic calcium. Calcium-channel blockers are commonly used as vasodilators for the treatment of hypertensive crises. There are three families of commercially available calcium-channel blockers: 1,4 dihydropyridines, phenylalkylamines, and benzothiazepines. These drugs block extracellular calcium entry through the L-type voltage-gated channel. Systemic vasodilation is produced as the cytosolic calcium level is lowered and myosin-actin contraction cannot be maintained. The precise mechanism of blockade and the tissue site selectivity varies among the three drug families. The 1,4 dihydropyridines are selective for the arteriolar beds, while the phenylalkylamines and benzothiazepines are selective for the atrioventricular node. Of the calcium-channel blockers, the dihydropyridines nifedipine and nicardipine are recommended as first-line agents for hypertensive emergencies and urgencies because of their peripheral arteriolar bed selectivity and their pharmacologic and kinetic profiles.

Acute Disease↗
PubMed1995

Remote communication from a mobile terminal: an adjunct for a computerized intensive care unit order management system.

OBJECTIVES: To develop and implement a fully mobile computer terminal that interfaces with our computerized intensive care unit (ICU) local area network and order management system. This system can provide access to the entire network and to order review and entry and during ICU bedside rounds. DESIGN: Descriptive report. SETTING: Surgical ICU in Department of Veterans Affairs Medical Center. SYSTEM CONFIGURATION: A parallel local area network was configured for the remote mobile computer system. A proprietary remote transmission system (Altair II, Motorola) was used. This high-throughput system minimizes interference and errors by using licensed, nonshared, radiofrequency spectra. CONCLUSION: The resulting mobile system is an economical and time-efficient adjunct to an established ICU computerized network and order management system. Clinical working bedside rounds are now routinely conducted with the mobile terminal, providing immediate access to full network resources.

Computer Terminals↗
PubMed1995

Today's strategies for treating postoperative hypertension. Immediate evaluation and targeted treatment are required.

Postoperative hypertension, though transient, requires immediate attention. Clinical variables include the patient's preoperative blood pressure, medications, and acute medical status; the surgical procedure performed; and the physiologic changes induced by surgery. Evaluate and treat any reversible causes of hypertension. Initiate drug therapy when organ failure or dysfunction is present or when the patient is at high risk for such complications. In choosing an agent, look for ease of administration, titratability of blood pressure response, rapid onset and cessation of action, and a low incidence of adverse effects. Options are nitrovasodilators, calcium channel blockers, ACE inhibitors, direct-acting vasodilators, adrenergic blockers, and neuromodulators (narcotics and anesthetics).

Adrenergic beta-Antagonists↗
PubMed1994

Federal and nationwide intensive care units and healthcare costs: 1986-1992.

OBJECTIVES: To establish Department of Veterans Affairs' intensive care unit (ICU) costs from a database and to use this information to validate the Russell equation, the most commonly used method of calculating ICU costs. To compare and trend Department of Veterans Affairs' and nationwide (USA) ICU and healthcare costs. DESIGN: Comparison study. SETTING: Database analysis of Department of Veterans Affairs' and nationwide ICUs over a 6-yr period (1986-1992), with biennial evaluations. MAIN MEASURES: Costs and bed occupancies of Department of Veterans Affairs' and nationwide hospitals and ICUs, as well as United States national health expenditures and gross domestic product. RESULTS: Fifty percent to Department of Veterans Affairs' ICU funds were used for nurse and physician salaries. Department of Veterans Affairs' ICU direct and indirect cost ratios have remained constant (2:1). The Russell equation is valid, providing that the "inpatient only" cost variable is used. ICU costs were consistently lower in the Department of Veterans Affairs' than nationwide, as compared by the Russell equation. A smaller fraction of the hospital budget was allocated to the ICU in the Department of Veterans Affairs than in nationwide institutions. Despite an increasing nationwide ICU patient workload, the percentage of ICU fund allocations has not increased. Health care in the United States increases at a rate greater than the increase in gross domestic product. Healthcare delivery costs are increasing at a greater rate nationwide than in the Department of Veterans Affairs. The percentage increase in ICU cost per day, both in the Department of Veterans Affairs and nationwide, was less than the increase in healthcare costs. The percent of the gross domestic product, national health expenditure, and hospital cost used by the ICU has increased minimally during the course of this study. CONCLUSIONS: The Department of Veterans Affairs has the only national ICU line item cost database available. For the Russell equation calculation to be accurate, inpatient only costs should be used. Until customized Health Care Financing Administration analyses become available, nationwide ICU costs are best determined by the Russell equation. Department of Veterans Affairs' ICUs have a consistent cost advantage over nationwide ICUs. Increases in United States healthcare delivery costs continue to exceed the increase in gross domestic product. Cost containment is already occurring in critical care.

Bed Occupancy↗
PubMed1994

Critical care medicine: observations from the Department of Veterans Affairs' intensive care units.

OBJECTIVES: To study the critical care medicine programs of the Department of Veterans Affairs. DESIGN: Survey study. SETTING: Data were obtained from 85% (113/133) of the acute care hospitals of the Department of Veterans Affairs. MAIN MEASURES: Intensive care unit (ICU) administrative and patient demographics, physician training and certification, participation in critical care medicine programs and research. RESULTS: Analyses were performed on 78% (2021) of Department of Veterans Affairs' ICU beds. Mortality (%) was highest in medical ICUs (11.7 +/- 0.8) and lowest in coronary care units (5.0 +/- 0.5) and surgical ICUs (5.5 +/- 0.5). The average length of stay (days) was highest in medical ICUs (5.6 +/- 0.6) and lowest in combined medical-coronary care units (4.2 +/- 0.4) and coronary care units (4.3 +/- 0.5). The majority of ICU directors have internal medicine training. A minority of ICU directors are formally trained in critical care medicine or are board eligible or certified in critical care medicine. The majority of fellows in the ICU are pulmonary or cardiac fellows; a minority are critical care medicine fellows. Accredited critical care medicine fellowship training programs were found in only 17% (19/113) of responding Department of Veterans Affairs' institutions. Seventy-three percent (82/113) of ICUs in responding hospitals had published fewer than five publications between 1987 and 1990. CONCLUSIONS: The results of this study suggest that the Department of Veterans Affairs would benefit from increasing the number of critical care medicine board eligible/certified directors, and increasing the program's participation in accredited critical care medicine fellowship training programs and research endeavors. Overall, however, we conclude that the Department of Veterans Affairs' critical care medicine program is at least comparable to nationwide ICUs in the parameters evaluated.

Critical Care↗