James W. Holcroft

Hemodynamic effects of increased abdominal pressure

Abstract The effect of increased abdominal pressure on cardiac output was analyzed by constructing cardiac function and venous return curves in anesthesized, ventilated dogs. Increasing abdominal pressure to 40 mm Hg by infusing fluid into the abdomen decreased cardiac output by 53% in hypervolemic dogs and by 17% in normovolemic dogs, but increased cardiac output by 50% in hypervolemic dogs. Left ventricular cardiac function curves were shifted downward with increased abdominal pressure, due, at least in part, to increased total peripheral resistance. Venous return curves were constricted by using a right heart bypass. Venous resistance rose from 8 to 17 mm Hg/liter/min with increase at high right atrial pressures. The effect of increased abdominal pressure on cardiac output results from the combined effects of changes in cardiac function and venous return, the direction and magnitude of which depend on intravascular volume and the level of abdominal pressure.

A comparison of several hypertonic solutions for resuscitation of bled sheep

Small volumes (4 ml/kg) of 2400 mOsm NaCl restore cardiac output and mean arterial pressure to 80% of baseline after hemorrhage (65% of blood volume) in unanesthetized sheep. An equal volume of normal saline is less effective. To identify an optimal hypertonic solution, we screened six 2400 mOsm solutions in 18 randomized experiments in 8 sheep: NaCl, NaHCO3, NaCl/sodium acetate, NaCl/mannitol, NaCl/6% Dextran 70, and glucose. Cardiovascular function, as determined by cardiac output and mean arterial pressure, was restored best with NaCl, NaCl/NaAc, and NaCl/Dex. These three solutions were then evaluated using 18 sheep in 36 experiments. Following a 1-hr baseline period, the sheep were bled to a mean arterial pressure of 50 mm Hg for 2 hr. One of the solutions was then given in a volume of 4 ml/kg over 2 min and the sheep were monitored for 3 hr. Within 3 min of the infusion, cardiac output increased to greater than 100% of baseline for all three solutions. The NaCl-Dex solution sustained a significantly higher cardiac output over the 3-hr observation period than the other solutions. Plasma volume increased for all solutions following infusion. NaCl-Dex maintained plasma volume significantly better than the other solutions. As a further control, an isotonic solution of 6% Dextran 70 in normal saline was studied. It was not as effective as the hypertonic NaCl-Dex in maintaining cardiac output, mean arterial pressure, or plasma volume. Osmolality increased 10% (309 to 326 mOsm/kg H2O), plasma [NA] increased 7% (151 to 161 meq/liter), and plasma [K] decreased from 3.9 to 2.6 meq/liter following the hypertonic infusions. The sheep appeared to tolerate these electrolyte changes well. We conclude that a single bolus infusion of 2400 mOsm NaCl with 6% Dextran 70 best resuscitates sheep that have been subjected to a moderate degree of hemorrhagic shock compared to several other solutions. Its beneficial effects are caused in part by a sustained reestablishment of plasma volume. More studies are needed to document the safety of dextran in the clinical setting of hemorrhagic shock. Small volumes of hypertonic solutions may be valuable in the initial fluid resuscitation of patients in hemorrhagic shock.

Individual patient cohort analysis of the efficacy of hypertonic saline/dextran in patients with traumatic brain injury and hypotension

BACKGROUND Resuscitation with hypertonic saline/dextran (HSD) has been suggested to be efficacious in patients who have traumatic brain injury and are hypotensive. We undertook a cohort analysis of individual patient data from previous prospective randomized double-blinded trials to evaluate improvements in survival at 24 hours and discharge after initial treatment with HSD in patients who had traumatic brain injury (head region Abbreviated Injury Score > or = 4) and hypotension (systolic blood pressure < or = 90 mm Hg). METHODS All variables and end points were defined before initiation of data handling. Investigators were blind as to the treatment. Case report forms were received from six studies. Of these, 223 patients met the inclusion for traumatic brain injury. Comparisons between HSD and standard of care were made using stratified analysis and logistic regression to assess efficacy, confounding, and interaction. Potential confounding variables of pre-fluid treatment, Glasgow Coma Scale score (3-8 vs. 9-15), injury type, and systolic blood pressure can be considered a priori factors that were known before randomization. Effects of the various trials was also considered. RESULTS Treatment with HSD resulted in a survival until discharge of 37.9% (39 of 103) compared with 26.9% (32 of 119) with standard of care (p = 0.080). Using logistic regression, adjusting for trial and potential confounding variables, the treatment effect can be summarized by the odds ratio of 2.12 (p = 0.048) for survival until discharge. CONCLUSIONS Patients who have traumatic brain injuries in the presence of hypotension and receive HSD are about twice as likely to survive as those who receive standard of care.

3% NaCl and 7.5% NaCl/dextran 70 in the resuscitation of severely injured patients.

Cardiovascular resuscitation of the severely injured patient in the field remains unsatisfactory because large volumes of intravenous fluid are needed to keep up with ongoing blood losses and because only small volumes of fluid can be given. In the first study reported here, small volumes (less than or equal to 12 mL/kg) of 3% NaCl were given to patients who were having surgery for severe injuries. The 3% NaCl restored blood pressure, pH, and urine output with approximately one half of the cumulative fluid requirement of patients who received isotonic fluids (p less than 0.05). In a second study, 7.5% NaCl/dextran 70, 250 mL, was given in a prospective, randomized, and double-blinded trial to injured patients in the field. Blood pressure in the hypertonic/hyperoncotic group increased 49 mmHg during transport (p less than 0.005); blood pressure in patients given lactated Ringers solution increased 19 mmHg (NS). Survival favored the hypertonic/hyperoncotic group. The 7.5% NaCl/dextran 70 solution appears particularly promising for treatment of injured patients in the field.

Improved predictions from a severity characterization of trauma (ASCOT) over Trauma and Injury Severity Score (TRISS): results of an independent evaluation

OBJECTIVE In 1986, data from 25,000 major trauma outcome study patients were used to relate Trauma and Injury Severity Score (TRISS) values to survival probability. The resulting norms have been widely used. Motivated by TRISS limitations, A Severity Characterization of Trauma (ASCOT) was introduced in 1990. The objective of this study was to evaluate and compare TRISS and ASCOT probability predictions using carefully collected and independently reviewed data not used in the development of those norms. DESIGN This was a prospective data collection for consecutive admissions to four level I trauma centers participating in a major trauma outcome study. MATERIALS AND METHODS Data from 14,296 patients admitted to the four study sites between October 1987 through 1989 were used. The indices were evaluated using measures of discrimination (disparity, sensitivity, specificity, misclassification rate, and area under the receiver-operating characteristic curve) and calibration [Hosmer-Lemeshow goodness-of-fit statistic (H-L)]. MEASUREMENTS AND MAIN RESULTS For blunt-injured adults, ASCOT has higher sensitivity than TRISS (69.3 vs. 64.3) and meets the criterion for model calibration (H-L statistic < 15.5) needed for accurate z and W scores. The TRISS does not meet the calibration criterion (H-L = 30.7). For adults with penetrating injury, ASCOT has a substantially lower H-L value than TRISS (20.3 vs. 138.4), but neither meets the criterion. Areas under TRISS and ASCOT ROC curves are not significantly different and exceed 0.91 for blunt-injured adults and 0.95 for adults with penetrating injury. For pediatric patients, TRISS and ASCOT sensitivities (near 77%) and areas under receiver-operating characteristic curves (both exceed 0.96) are comparable, and both models satisfy the H-L criterion. CONCLUSIONS In this age of health care decisions influenced by outcome evaluations, ASCOTs more precise description of anatomic injury and its improved calibration with actual outcomes argue for its adoption as the standard method for outcome prediction.

Prostaglandin E1 and survival in patients with the adult respiratory distress syndrome. A prospective trial

A 7-day infusion of prostaglandin E1 (PGE1), an immunomodulator, was evaluated in a prospective, randomized, placebo-controlled, double-blinded trial in surgical patients with the adult respiratory distress syndrome (ARDS). The drug seemed to improve pulmonary function—only two PGE1 patients died with severe pulmonary failure compared with nine placebo patients (p = 0.01). Survival at 30 days after the end of the infusion— the predetermined end point of the study—was significantly better in the patients given PGE1 (p = 0.03), with 15 of 21 PGE1 patients (71%) alive at this time compared with seven of 20 placebo patients (35%). Improvement in overall survival in the PGE, patients did not reach statistical significance (p = 0.08). Overall survival in patients initially free of severe organ failure, however, was significantly better in the PGE, patients (p = 0.03). Of the six PGE1 patients free of severe organ failure at time of entry, all survived to leave the hospital; of the 10 placebo patients initially free of severe organ failure, four survived. The drug had no serious side effects and did not potentiate susceptibility to infection. PGE1 is a promising agent for the treatment of ARDS.

A prospective, randomized trial limiting perioperative red blood cell transfusions in vascular patients

BACKGROUND Patients undergoing major arterial reconstruction have traditionally been transfused with red blood cells to keep hemoglobin concentrations above 10 g/dL in order to prevent anemia-induced myocardial ischemia. There are no data to support this practice. The hypothesis that vascular patients will tolerate a hemoglobin concentration of 9 g/dL was examined. METHODS Ninety-nine patients undergoing elective aortic and infrainguinal arterial reconstructions were prospectively randomized preoperatively to receive transfusions to maintain a hemoglobin level of either 10 g/dL or 9 g/dL. RESULTS Despite significantly different postoperative hemoglobin levels of 11.0 +/- 1.2 versus 9.8 +/- 1.3 g/dL (P <0.0001), there were no differences in mortality or cardiac morbidity rates or length of hospital stay. There were no differences in hemodynamic parameters. Oxygen delivery was lower in the group with lower hemoglobin levels, but there was no difference in O2 consumption between the groups. CONCLUSIONS A lower hemoglobin concentration was tolerated without adverse clinical outcome. Patients did not compensate for anemia by increased myocardial work, but by increasing O2 extraction in the peripheral tissues.

Infusion of very hypertonic saline to bled rats: Membrane potentials and fluid shifts

Anesthetized rats were subjected to a moderate degree of hemorrhagic shock, lowering their mean arterial pressure to approximately 50 mm Hg for approximately 100 min. At the end of the shock period, resting skeletal muscle transmembrane potentials had depolarized from a baseline value of -82 mV to -65 mV; intracellular water had increased by 13%; and intracellular sodium and chloride contents had doubled. Eight rats were then given an infusion of very hypertonic saline (2400 mOsmole/kg, calculated osmolality) in a volume equal to only 10% of the volume of shed blood; another eight rats were given the equivalent amount of sodium and chloride in an isotonic solution (volume equal to 80% of shed blood). The mean arterial pressure in the rats that were given the very hypertonic saline returned to 81 mm Hg, compared to 55 mm Hg in the animals given normal saline. The membrane potentials in the hypertonic group polarized back to near normal- -78 mv--compared to no changes in the normal saline group. Intracellular water returned to preshock values in the hypertonic group as did intracellular sodium and chloride contents. Cellular contents in the normal saline group remained at shock levels. It was concluded that, in rats, infusion of small amounts of hypertonic saline can reverse some of the cellular abnormalities induced by hemorrhagic shock.

Immediate external fixation of unstable pelvic fractures

Immediate external fixation has been proposed as a means of stabilizing severe pelvic fractures to reduce the chance of organ failure and death. Sixty-six patients were admitted from January 1980 through December 1983 with double fractures of the pelvic ring that involved the posterior elements. Twenty-six patients (39 percent) underwent immediate external fixation for instability, and 40 patients (61 percent) with stable fractures were treated with bed rest. The two groups were similar in age, injury severity score, and degree of shock. The mortality rate of the two groups was the same (12 percent), as was the incidence of organ failure. The mean transfusion requirement in the unstable group was greater, but not significantly. Our results were better than those reported in recent studies in which immediate rigid fixation was not used. We conclude that the patient with multiple trauma without unstable pelvic fracture should undergo immediate external fixation to decrease morbidity and mortality rates and limit soft tissue damage.

Extravascular Lung Water Following Hemorrhagic Shock in the Baboon: Comparison Between Resuscitation with Ringer's Lactate and Plasmanate

Baboons were subjected to deep hemorrhagic shock by using a membrane potential of -65 mv as an endpoint. They were then resuscitated with either Plasmanate plus their shed blood or Ringers lactate plus their shed blood. As compared with their own preshock values, the Plasmanate-resuscitated animals accumulated more extravascular lung water than the Ringers lactate-resuscitated animals. Another group of baboons resuscitated from deep shock demonstrated significant extravasation of albumin on postmortem analysis of lung composition. This increased tendency for extravasation of albumin after shock partially explains why resuscitation with Plasmanate gave no protection against the formation of pulmonary edema. The authors believe that Plasmanate, and probably other colloidal solutions, should be used sparingly in the initial treatment of deep hemorrhagic shock.