R. Russell Martin

Immediate versus Delayed Fluid Resuscitation for Hypotensive Patients with Penetrating Torso Injuries

Background Fluid resuscitation may be detrimental when given before bleeding is controlled in patients with trauma. The purpose of this study was to determine the effects of delaying fluid resuscitation until the time of operative intervention in hypotensive patients with penetrating injuries to the torso. Methods We conducted a prospective trial comparing immediate and delayed fluid resuscitation in 598 adults with penetrating torso injuries who presented with a prehospital systolic blood pressure ≤ 90 mm Hg. The study setting was a city with a single centralized system of prehospital emergency care and a single receiving facility for patients with major trauma. Patients assigned to the immediate-resuscitation group received standard fluid resuscitation before they reached the hospital and in the trauma center, and those assigned to the delayed-resuscitation group received intravenous cannulation but no fluid resuscitation until they reached the operating room. Results Among the 289 patients who received...

Abbreviated laparotomy and planned reoperation for critically injured patients.

The triad of hypothermia, acidosis, and coagulopathy in critically injured patients is a vicious cycle that, if uninterrupted, is rapidly fatal. During the past 7.5 years, 200 patients were treated with unorthodox techniques to abruptly terminate the laparotomy and break the cycle. One hundred seventy patients (85%) suffered penetrating injuries and 30 (15%) were victims of blunt trauma. The mean Revised Trauma Score, Injury Severity Score, and Trauma Index Severity Score age combination index predicted survival were 5.06%, 33.2%, and 57%, respectively. Resuscitative thoracotomies were performed in 60 (30%) patients. After major sources of hemorrhage were controlled, the following clinical and laboratory mean values were observed: red cell transfusions--22 units, core temperature--32.1 C, and pH--7.09. Techniques to abbreviate the operation included the ligation of enteric injuries in 34 patients, retained vascular clamps in 13, temporary intravascular shunts in four, packing of diffusely bleeding surfaces in 171, and the use of multiple towel clips to close only the skin of the abdominal wall in 178. Patients then were transported to the surgical intensive care unit for vigorous correction of metabolic derangements and coagulopathies. Ninety-eight patients (49%) survived to undergo planned reoperation (mean delay 48.1 hours), and 66 of 98 (67%) survived to leave the hospital. With the exception of intravascular shunts, there were survivors who were treated by each of the unorthodox techniques. Of 102 patients who died before reoperation 68 (67%) did so within 2 hours of the initial procedure. Logistic regression showed that red cell transfusion rate and pH may be helpful in determining when to consider abbreviated laparotomy. The authors conclude that patients with hypothermia, acidosis, and coagulopathy are at high risk for imminent death, and that prompt termination of laparotomy with the use of the above techniques is a rational approach to an apparently hopeless situation.

Induction of Aryl Hydrocarbon Hydroxylase in Human Pulmonary Alveolar Macrophages by Cigarette Smoking

Abstract Pulmonary alveolar macrophages were obtained from healthy volunteers by saline pulmonary lavage, and aryl hydrocarbon hydroxylase was measured in the cells. Enzyme activity was low in cells from five nonsmokers with a mean of 0.008±0.004 U/106 cells. Cells obtained from nine cigarette smokers contained higher enzyme levels, with a mean of 0.095±0.024 U/106 cells. A former cigarette smoker was lavaged on five occasions. Enzyme activity during two lavages 4 mo apart were 0.010 and 0.009 U/106 cells, respectively. 1 wk after smoking was resumed, the enzyme activity rose slightly to 0.013, and reached 0.041 U/106 cells by 1 mo. Upon cessation of smoking, the enzyme activity returned to control levels by the next lavage, 2 mo later. These data indicate that aryl hydrocarbon hydroxylase may be induced in pulmonary alveolar macrophages of subjects chronically exposed to cigarette smoke.

Pharmacokinetics of an anti-human immunodeficiency virus antisense oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected subjects

Human pharmacokinetics of an antisense oligodeoxynucleotide phosphorothioate (GEM 91) developed as an anti—human immunodeficiency virus (HIV) agent was carried out in this study. 35S‐Labeled GEM 91 was administered to six HIV‐infected individuals by means of 2‐hour intravenous infusions at a dose of 0.1 mg/kg. Plasma disappearance curves for GEM 91—derived radioactivity could be described by the sum of two exponentials, with half‐life values of 0.18 ± 0.04 and 26.71 ± 1.67 hours. The radioactivity in plasma was further evaluated by polyacrylamide gel electrophoresis, showing the presence of both intact GEM 91 and lower molecular weight metabolites. Urinary excretion represented the major pathway of elimination, with 49.15% ± 6.80% of the administered dose excreted within 24 hours and 70.37% ± 6.72% over 96 hours after dosing. The radioactivity in urine was associated with lower molecular weight metabolites. No drug‐related toxicity was observed.

Prospective evaluation of preoperative fluid resuscitation in hypotensive patients with penetrating truncal injury: A preliminary report

Although intravenous (IV) fluid therapy is routinely prescribed for hypotensive injury victims, there are concerns that elevating the blood pressure before hemorrhage is controlled may be detrimental. This is a preliminary report of an ongoing randomized study designed to evaluate the effect fluid resuscitation, delayed until surgical intervention, has on the outcome for hypotensive victims of penetrating truncal injury. In the first year, 300 consecutive patients with gunshot or stab wounds to the trunk who had a systolic blood pressure of 90 mm Hg or less were entered into the study. Patients were excluded from the outcome analysis because of death at the scene or minor injury not requiring surgical intervention. The remaining study patients were randomized into (1) an immediate resuscitation group (n = 96) for whom IV fluid resuscitation was initiated in the ambulance and in the emergency center before surgical intervention, or (2) a delayed resuscitation group (n = 81) for whom IV fluid resuscitation was delayed until the time of surgical intervention. The two study groups were found to be well balanced with respect to anatomic injury severity, pretreatment vital signs, survival probability, and preoperative treatment times. There were no significant differences in the rate of survival to hospital discharge (immediate resuscitation group, 56%; delayed resuscitation group, 69%). There were no significant differences in the rate of postoperative complications. Further study is necessary to determine if it is advantageous to delay fluid resuscitation until surgical intervention.

Hemophilus influenzae pneumonia in adults.

Hemophilus influenzae pneumonia was diagnosed in 41 adult patients based on cultures of blood, pleural fluid or transtracheal aspirate. Bacteremia occurred in all age groups, but was most frequent in patients over the age of 50 years with severe underlying pulmonary disease. Chest films usually demonstrated multisegmental or multilobar infiltrates without evidence of cavitation. Pleural involvement was evident in half of the patients, although empyema occurred infrequently. Mortality was almost always associated with serious underlying diseases and bacteremia. Encapsulated strains of H. influenzae (usually type B) were identified in 18 of 22 (82 per cent) patients. The use of transtracheal aspirations and the adoption of routine subculturing of blood cultures on chocolate agar appear to be important factors in our increased recognition of this disease.

Pharmacokinetics of cefepime after single and multiple intravenous administrations in healthy subjects.

The pharmacokinetics of cefepime in 31 young, healthy volunteers were assessed after the administration of single and multiple 250-, 500-, 1,000-, or 2,000-mg intravenous doses. Each subject received a single dose of cefepime via a 30-min intravenous infusion on day 1 of the study. Starting from day 2, subjects received multiple doses of cefepime every 8 h for 9 days, and on the morning of day 11, they received the last dose. Serial blood and urine samples were collected after administration of the first dose and on days 1, 6, and 11. Cefepime concentrations in plasma and urine were assayed by using reverse-phase high-performance liquid chromatography with UV detection. Data were evaluated by noncompartmental methods to determine pharmacokinetic parameters. The mean half-life of cefepime was approximately 2 h and did not vary with the dose or duration of dosing. The regression analyses of peak levels (Cmax) in plasma at the end of the 30-min intravenous infusion and the area under the plasma concentration-versus-time curve (AUCo-infinity) showed a dose-proportional response. The steady-state volume of distribution (Vss) was approximately 18 liters and was independent of the administered dose. The multiple-dose pharmacokinetic data are suggestive of a lack of accumulation or change in clearance of cefepime on repeated dosing. Cefepime was excreted primarily unchanged in urine. The recovery of intact cefepime in urine was invariant with respect to the dose and accounted for over 80% of the dose. The values for renal clearance ranged from 99 to 132 ml/min and were suggestive of glomerular filtration as the primary excretion mechanism. It is concluded that cefepime linear pharmacokinetics in healthy subjects.

Immunoglobulin Secreting Cells in Normal Human Bronchial Lavage Fluids

Immunoglobulin secreting cells were quantitated in the bronchial lavage fluids of 12 normal volunteers and compared with immunoglobulin secreting cells in peripheral blood, by a reverse hemolytic plaque assay. The mean number of cells secreting immunoglobulin (Ig)G in bronchial lavage fluids was 489 per million lymphocytes vs. a mean of 175 IgG secreting cells per million lymphocytes in peripheral blood (P < 0.02). The mean number of IgA secreting cells in bronchial lavage fluids was 633 per million lymphocytes as compared to 100 per million lymphocytes in peripheral blood (P < 0.005). Thus, compared to peripheral blood, cells from the lavage fluids were relatively enriched for both IgG and IgA secreting cells. However, IgA secreting cells were the major class of immunoglobulin secreting cells in bronchial lavage fluids, whereas IgG secreting cells predominated in peripheral blood. The prominence of IgA secreting cells in bronchial lavage fluids was further demonstrated by a mean ratio of IgA/IgG secreting cells in bronchial lavage fluids of 1.26 compared to a ratio in peripheral blood of 0.57 (P < 0.02). Cells secreting IgM were identified in only four of seven bronchial lavage fluid samples studied but in all peripheral blood samples. IgE secreting cells were not present in normal peripheral blood but could be demonstrated in 5 of 11 lavage fluid specimens. Thus, cells actively secreting immunoglobulins can be identified in the lower bronchial-alveolar tree of normal human subjects. Cells secreting IgG, IgA, or IgM may function in local lung defenses against infection; cells secreting IgE may contribute to hypersensitivity reactions in the lung.

Guidelines for the prevention of infection after combat-related injuries.

Management of combat-related trauma is derived from skills and data collected in past conflicts and civilian trauma, and from information and experience obtained during ongoing conflicts. The best methods to prevent infections associated with injuries observed in military combat are not fully established. Current methods to prevent infections in these types of injuries are derived primarily from controlled trials of elective surgery and civilian trauma as well as retrospective studies of civilian and military trauma interventions. The following guidelines integrate available evidence and expert opinion, from within and outside of the US military medical community, to provide guidance to US military health care providers (deployed and in permanent medical treatment facilities) in the diagnosis, treatment, and prevention of infections in those individuals wounded in combat. These guidelines may be applicable to noncombat traumatic injuries under certain circumstances. Early wound cleansing and surgical debridement, antibiotics, bony stabilization, and maintenance of infection control measures are the essential components to diminish or prevent these infections. Future research should be directed at ideal treatment strategies for prevention of combat-related injury infections, including investigation of unique infection control techniques, more rapid diagnostic strategies for infection, and better defining the role of antimicrobial agents, including the appropriate spectrum of activity and duration.

Safety, tolerance, and pharmacokinetic evaluation of cefepime after administration of single intravenous doses.

In this double-blind, single-dose phase I study, the safety and tolerance of cefepime were assessed in 24 healthy male subjects, with ceftazidime as the control drug. Four subjects in each of the six dose groups (62.5, 125, 250, 500, 1,000, or 2,000 mg as a 30-min intravenous infusion) received each antibiotic, according to a crossover design, with a 2-day washout period between treatments. Blood and urine samples were obtained to characterize the pharmacokinetics of cefepime. Plasma and urine samples were assayed for intact cefepime. Samples containing ceftazidime were discarded. The adverse effects observed in the study were mild and infrequent, with prompt recovery from adverse experiences and abnormal laboratory values. The cefepime pharmacokinetic parameters for the therapeutically significant doses of 250 to 2,000 mg appeared to be proportional to dose and similar to literature values for ceftazidime. The elimination half-life of about 2 h was independent of the dose. Urinary recovery of intact cefepime was invariant with respect to dose; an overall mean value of 82% of dose was obtained for the four highest levels. Mean renal clearance was 105 ml/min and suggestive of glomerular filtration as the primary excretion mechanism. In normal humans, the safety and pharmacokinetic profiles of cefepime are very similar to those of ceftazidime.