Kenneth Waxman

Lactated Ringer's solution resuscitation causes neutrophil activation after hemorrhagic shock

PURPOSE To determine the degree of neutrophil activation caused by hemorrhagic shock and resuscitation. METHODS Awake swine underwent 15-minute 40% blood volume hemorrhage, and a 1-hour shock period, followed by resuscitation with: group I, lactated Ringers solution (LR); group II, shed blood; and group III, 7.5% hypertonic saline (HTS). Group IV underwent sham hemorrhage and LR infusion. Neutrophil activation was measured in whole blood using flow cytometry to detect intracellular superoxide burst activity. RESULTS Neutrophil activation increased significantly immediately after hemorrhage, but it was greatest after resuscitation with LR (group I, 273 vs. 102%; p < 0.05). Animals that received shed blood (group II) and HTS (group III) had neutrophil activity return to baseline state after resuscitation. Group IV animals had an increase in neutrophil activation (259 vs. 129%; p < 0.05). CONCLUSION Neutrophil activation occurring after LR resuscitation and LR infusion without hemorrhage, but not after resuscitation with shed blood or HTS, suggests that the neutrophil activation may be caused by LR and not by reperfusion.

Clinical trial of survivors' cardiorespiratory patterns as therapeutic goals in critically ill postoperative patients.

The hypothesis was tested that the median values of survivors of life-threatening postoperative conditions, rather than the norms of unstressed healthy volunteers, are the appropriate therapeutic goals for critically ill postoperative patients. The authors studied prospectively a series of 100 consecutive critically ill postoperative patients; normal values were used as the therapeutic goals of the control patients, while the median values of survivors were used as the goals of therapy for the protocol group. The age, sex, primary illness, surgical operation, lowest mean arterial pressure (MAP), time in hypotension incidence of severe hypotension (MAP greater than 50 mm Hg), and presence of associated severe medical illnesses (defined by predetermined criteria) were comparable in the control and protocol groups; i.e., clinical conditions of the protocol group were at least as severe as those of the control group. The mortality was significantly less in the protocol group (13%) than in the control group (48%); the number of life-threatening complications were also greater in the control group. These data suggest that the cardiorespiratory pattern of survivors are the appropriate goals of therapy for critically ill patients.

Effects of hypoxia and shock on transcutaneous PO2 values in dogs.

Transcutaneous Po2 (PtcO2) was measured with transcutaneous oxygen electrode sensors and correlated with Pao2, Pvo2, cardiac output, and O2 delivery during changes in FIO2 and standardized hypovolemic shock in anesthetized dogs. Simultaneously, cardiorespiratory variables were measured: intravascular pressures, arterial and mixed venous gases, and cardiac output. Before the shock experiments, these physiologic variables were measured while the FIO2 was varied from 0.21–1.0. Then the FIO2 was held constant while the animal was subjected to hemorrhagic shock and resuscitation. PtcO2 followed PaO2 values (r = 0.96) during variations in the FIO2 when the cardiac output was in the normal range. The 95% response time was less than 15 sec. In the active hemorrhage stage, PtcO2, Pvo2, and cardiac output simultaneously decreased. As the cardiac output dropped, the PtcO2 fell from values near that of the PaO2 and approached the falling PvO2. At the point of 20 torr, the PtcO2 fell below the PvO2. During these shock experiments, when the PtcO2 was greater than 20 torr, the PvO2 was less than PtcO2, but when the PtcO2 was less than 20 torr, the PvO2 was greater than the PtcO2. This PtcO2-PvO2 crossing point corresponded to a cardiac output of 25–30% of the control and a decrease in total body oxygen consumption of 30%. With fluid resuscitation, the PtcO2 responded more quickly at first than the increase in cardiac output. Throughout the shock period, the PaO2 did not vary significantly from the preshock control value. The oxygen delivery was the variable that the PtcO2 followed most closely during the entire hypoxia and hemorrhagic shock experiments, rw = 0.82.It was concluded that the PtcO2 is an accurate, noninvasive, continuous method for monitoring peripheral oxygen delivery and a valuable tool for the study of disturbed circulation in various shock states. In the latter conditions, it does not follow PaO2, but rather, oxygen delivery.

Cardiovascular Effects of Anesthetic Induction with Ketamine

Anesthetic induction with ketamine has been reported to maintain or improve cardiovascular performance in severely ill patients. Using invasive cardiovascular monitoring, we studied physiologic responses to a single dose of ketamine in 12 critically ill patients. Six patients demonstrated decreases in ventricular contractility, and four had decreases in cardiac output. Mean arterial blood pressure decreased in four patients. Pulmonary venous admixture increased in four of six patients, while oxygen consumption decreased in eight of 11 patients. Thus, a single dose of ketamine produced decreases in cardiac and pulmonary performance and in peripheral oxygen transport in this group of patients. It is proposed that in severely ill patients, preoperative stress may alter the usual physiologic responses to ketamine administration, and adverse effects may predominate. Ketamine, therefore, should be used with caution for induction of anesthesia in critically ill and in acutely traumatized patients until additional studies and further information on cardiovascular responses to ketamine are available.

Adequate resuscitation of burn patients may not be measured by urine output and vital signs.

Objective.To compare vital sign and urine output monitoring of seriously burned patients with invasive monitoring during early resuscitation.Design.Retrospective review.Setting.A university hospital burn unit.Patients.Fourteen seriously burned patients who had pulmonary arterial monitoring. Monitori

Continuous transcutaneous oxygen monitoring during respiratory failure, cardiac decompensation, cardiac arrest, and CPR. Transcutaneous oxygen monitoring during arrest and CPR.

The transcutaneous oxygen sensor (PtcO2), which has been used to predict PaO2 in neonates, recently has been shown to follow changes in oxygen delivery, rather than PaO2 during shock and hypoxia in dogs. Six preterminal patients were continuously monitored with PtcO2 and monitored hemodynamically at frequent intervals during cardiac decompensation, arrest, and cardiopulmonary resuscitation (CPR). The weighted mean correlation coefficients between PtcO2 and O2 delivery as well as between PtcO2 and cardiac output were 0.94 and 0.96, respectively. Five patients died of severe ARDS and 1 patient died intraoperatively of hemorrhagic shock. Four patients were monitored 1–7 days before shock occurred. The correlation between PtcO2 and PaO2 was 0.91 during periods of normal cardiac output in the preterminal period. During cardiac decompensation, the cardiac output, PtcO2, and mixed venous oxygen tension (PvO2), all fell simultaneously. When a PtcO2 of 25 torr was reached, the PtcO2 fell below the PvO2. This also corresponded to a decrease in VO2. The mean VO2 was 142 ± 24 ml/min M2 for PtcO2 values >25 torr, and 75 ± 15 ml/min M2 for PtcO2 <25 torr (p<0.01). A PtcO2 of >40 torr corresponded to normal cardiac index, O2 delivery, VO2, PvO2, and arterial pH (pHa) while a PtcO2, of <25 torr corresponded to large reductions of these variables. A PtcO2 of <25 torr preceded cardiac arrest by 43 ± 28 min.

Predicting Performance on the American Board of Surgery Qualifying and Certifying Examinations: A Multi-institutional Study

BACKGROUND We sought to determine whether US Medical Licensing Examination (USMLE) Step 1 score, American Board of Surgery (ABS) In-Training Examination (ABSITE) score, and other variables are associated with failing the ABS qualifying and certifying examinations. Identifying such factors may assist in the early implementation of an academic intervention for at-risk residents. DESIGN Retrospective review. SETTING Seventeen general surgery training programs in the western United States. PARTICIPANTS Six hundred seven residents who graduated in 2000-2007. MAIN OUTCOME MEASURES First-time pass rates on the qualifying and certifying examinations, US vs non-US medical school graduation, USMLE Steps 1 and 2 scores, ABSITE scores, operative case volume, fellowship training, residency program type, and mandatory research. RESULTS The first-time qualifying and certifying examination pass rates for the 607 graduating residents were 78% and 74%, respectively. On multivariable analysis, scoring below the 35th percentile on the ABSITE at any time during residency was associated with an increased risk of failing both examinations (odds ratio, 0.23 [95% confidence interval, 0.08-0.68] for the qualifying examination and 0.35 [0.20-0.61] for the certifying examination), as was scoring less than 200 on the USMLE Step 1 (0.36 [0.21-0.62] for the qualifying examination and 0.62 [0.42-0.93] for the certifying examination). A mandatory research year was associated with an increased likelihood of passing the certifying examination (odds ratio, 3.3 [95% confidence interval, 1.6-6.8]). CONCLUSIONS Residents who are more likely to fail the ABS qualifying and certifying examinations can be identified by a low USMLE Step 1 score and by poor performance on the ABSITE at any time during residency. These findings support the use of the USMLE Step 1 score in the surgical residency selection process and a formal academic intervention for residents who perform poorly on the ABSITE.

Hemodynamic, blood volume, and oxygen transport responses to albumin and hydroxyethyl starch infusions in critically ill postoperative patients

Hemodynamic, plasma volume, and oxygen transport effects were measured after administration of 500 ml of 5% albumin or 6% hydroxyethyl starch (HES) in hypovolemic postoperative patients using a prospectively randomized crossover design. Both agents produced marked and significant improvement in plasma volume and flow as well as small transient increases in arterial and venous pressures, urine output, colloidal osmotic pressure (COP), and oxygen transport. The authors conclude that HES is a safe, inexpensive, effective plasma expander that has hemodynamic effects similar to those of other colloids.It was apparent from these and other studies that clinically stable postoperative patients may have appreciable blood volume deficits. Routine vital signs correlated poorly with the preinfusion control hemodynamic values or the changes in blood volume status after volume loading. Normal cardiac output, central venous pressure (CVP), and pulmonary arterial wedge pressure (WP) values are commonly seen in critically ill postoperative patients who, nevertheless, may be hypovolemic. Measurement of changes in these variables after a fluid challenge a useful way to assess plasma volume status.

Impaired oxygenation of gastric mucosa in portal hypertension

Increased susceptibility to mucosal damage is a prominent feature of portal hypertensive gastropathy. Since the portal hypertensive gastric mucosa has extensive microvascular changes, we postulated that the increased sensitivity to mucosal damage could have an ischemic basis. We measured distribution of gastric serosal and mucosal oxygenation in a group of portal hypertensive and sham-operated rats, and then studied the effects of intragastric aspirin. In the basal state, gastric mucosa of portal hypertensive rats had significantly reduced oxygenation compared to controls (24±5 vs 45±7 mm Hg PO2,P < 0.02), while serosal oxygenation was similar between the two groups. Intragastric aspirin produced significantly greater mucosal damage to portal hypertensive rats and mucosal oxygenation was almost one third that of sham-operated controls. Systemic arterial pressures and oxygenation were similar between the two groups. We conclude that there is impairment of gastric mucosal oxygenation and increased mucosal damage by aspirin in portal hypertensive rats compared with sham-operated controls. These results support our hypothesis that the increased sensitivity of the portal hypertensive mucosa to damage is a consequence of impaired mucosal oxygenation.

Trauma causes early release of soluble receptors for tumor necrosis factor

The importance of tumor necrosis factor (TNF) in the pathophysiology of trauma and hemorrhagic shock is not known. In addition, TNF bioactivity may be modulated by soluble forms of the 55-kd and 75-kd membrane receptors (TNFR). This study was undertaken to determine circulating levels of TNF and TNFR after trauma. Nine severely injured male patients were studied. The mean age was 30 +/- 10 years (range, 15-45). The mean Injury Severity Score (ISS) was 31.3 +/- 17.6 (range, 10-59), and the mean Revised Trauma Score (RTS), 5.7 +/- 2.2 (range, 0.7-7.8). Serum was obtained immediately upon arrival at our trauma center, within 1 hour of injury. The TNF and TNFR levels in the serum were measured using ELISA techniques. After trauma, 55-kd and 75-kd TNFR levels were significantly elevated above those of controls (6.99 +/- 4.57 ng/mL and 5.42 +/- 1.88 ng/mL, respectively, p < 0.01); TNF levels were not increased. Patient serum containing TNFR inhibited in vitro TNF cytotoxicity and correlated with 55-kd TNFR levels (p < 0.05). We conclude that TNF is a strong releasing factor for TNFR; the presence of TNFR may be indirect evidence that TNF is present after trauma, despite low measured levels. Both TNF and TNFR may be more important in trauma and hemorrhagic shock than previously thought.