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Sepsis is a leading cause of death following major trauma and complicated abdominal surgery. Tumor necrosis factor-alpha (TNF) is believed to be a central mediator in the inflammatory response syndrome. Numerous methods of blunting the TNF response in sepsis have been attempted with suggestion of increased survival and decreased organ injury. Thalidomide, shown in vitro to selectively inhibit TNF production, has been used clinically in states of chronic TNF elevation with encouraging results. In this study, we examined the effect of thalidomide administration in a rat model of acute septic shock. Femoral artery cannulation was performed and baseline TNF measured. Dose response was determined by giving varying doses of thalidomide by gavage. Rats were injected intraarterially with endotoxin and serial samples drawn. TNF was measured by ELISA. For survival, thalidomide was given by gavage and endotoxin injected intraperitoneally. Serum TNF elevation occurred after endotoxin injection with peak levels at 90 min. Thalidomide treated rats had lower TNF levels at all time points (P =0.01 at 90 and 120 min), with the inhibition being dose dependent. Survival in treated rats exceeded that of untreated rats (53% vs 19%, P =0.05) at 48 and 72 hr. In conclusion, we found that thalidomide administration leads to increased survival following acute endotoxemia, which may be due to the observed TNF inhibition.

One hundred consecutive trauma patients who underwent planned emergency intubation with muscle paralysis in the ED were studied to investigate the safety of these procedures and to determine their impact on the evaluation of patients with suspected head injury. Patients were intubated by either a surgeon (n = 47) or anesthesiologist (n = 53), and paralyzed with either vecuronium (n = 59) or succinylcholine (n = 41). Nasal intubation was used in 40 patients, oral in 57, and cricothyroidotomy in three. Ninety-four patients with suspected head injuries had a CT scan performed. Fifty-five (59%) had a positive scan and 15 required emergent neurosurgical intervention. Only two patients had lateral cervical spine roentgenograms before intubation; seven patients were eventually found to have cervical fractures. No patient suffered a neurologic deficit. One patient developed aspiration pneumonia following intubation. The three failed intubations occurred in patients with multiple facial fractures. We conclude that induced paralysis and intubation in the ED is safe, can facilitate the diagnostic workup, and may be a potentially life-saving maneuver in combative trauma patients.

Laboratory rats in profound hemorrhagic shock, but minimally restrained and unanesthetized, were exposed to 915 MHz microwave energy to rewarm the core tissues, which were cooled by approximately 4OC to 6OC during shock The survival rate of the animals that were rewarmed during the postshock period, after resuscitation was affected, was significantly higher than the survival rate of the animals that were rewarmed during shock, prior to resuscitation, and higher as well than the control group of shocked animals in whom no thermal intervention was attempted.

Hemorrhagic shock has been demonstrated to increase the susceptibility to bacterial infection [1–5]. Infection rates in patients who had sustained hemorrhagic shock complicating penetrating abdominal injury have been shown to be two to three times that for normotensive patients [4, 5]. Esrig demonstrated that a sublethal injection of endotoxin (lipopolysaccharide, LPS) resulted in significant mortality in rats following hemorrhagic shock [1]. This increased susceptibility to infection has been documented to persist for several days following shock in both rodent and murine models [2, 3]. Shock has also been demonstrated to result in numerous alterations in both cell-mediated and humoral immunity [3, 6, 7]. Among these is the failure of the bone marrow to mount a normal myelopoietic response to a challenge of intraperitoneal LPS following shock [8]. We have demonstrated that rats challenged with LPS after hemorrhagic shock resulted in a decline in the number of bone marrow granulocyte-macrophage colony-forming units (CFU-GM) compared with un-shocked rats [8]. Simultaneous with the loss of normal myelopoiesis is the appearance of serum factors inhibitory to CFU-GM growth.

Thirty-nine hemodynamically stable trauma patients were evaluated prospectively by laparoscopy before planned celiotomy. Laparoscopy was performed using a forward-viewing laparoscope connected to two high-resolution video monitors. The mechanism of injury was blunt trauma in eight, stab wounds (SWs) in 16, and gunshot wounds (GSWs) in 15. Laparoscopy correctly identified the presence of an intraperitoneal injury in 26 patients. Six other patients had retroperitoneal injuries, five of which were seen on laparoscopy. The remaining seven patients had no demonstrable intraperitoneal or retroperitoneal injuries, did not undergo celiotomy, and were observed without morbidity. In comparison with findings at surgery, laparoscopy identified injuries to the liver in eight of ten, to the diaphragm in three of three, to the colon in two of three, to the stomach in three of three, to the kidney in one of one, to the spleen in none of three, and to the small bowel in none of four patients. Visualization of the spleen was achieved in only one patient. The extent of the hemoperitoneum was underestimated from the laparoscopic examination in all nine patients with greater than 750 mL of peritoneal blood, four of whom had undetected active bleeding. Laparoscopy was performed easily in all patients and there were no complications associated with its use. In conclusion, the absence of an intra-abdominal injury was correctly identified with laparoscopy in 11 patients and laparoscopy may decrease the need for celiotomy in selected patients. However, the inability to "run the small bowel," visualize the spleen, and evaluate hemorrhage limits the utility of laparoscopy in determining which patients with laparoscopically visualized injuries will require celiotomy.

In recent research, hemorrhagic shock and septic shock have been studied as two separate entities. We have developed a treated model of hemorrhagic shock in which unrestrained and unanesthetized rats are bled to a mean arterial pressure of 30 torr until 80% of the maximum shed volume must be returned. Rats are maintained preshock and treated post shock with a 20% glucose-electrolyte solution. Survival of these animals is 62% at 24 hours post shock and all animals are dead at 72 hours post shock. Blood cultures obtained during shock become positive at 2 hours into the shock period and are significant compared to controls at 3 to 5 hours of shock (p less than 0.0001). Blood cultures obtained after the period of shock are significantly positive at 24 and 48 hours post shock (p less than 0.05) compared to controls. Intrashock cultures are monomicrobial; the majority of post-shock cultures are polymicrobial. All cultured organisms are normal rat enteric flora. Histologic changes of renal failure are also demonstrated post shock. We suggest that bacterial invasion, possibly from the gut, plays a role in the sepsis seen in patients following severe hemorrhagic shock. Sepsis may precede rather than follow the immune incompetence which accompanies shock.

Infusion of prostaglandin E1 is known to exert a beneficial effect in hemorrhagic shock. It is also known that hemorrhagic shock lowers hepatic stores of high-energy phosphates and that restoration of hepatic ATP is associated with improved organ function and survival. The present study was undertaken to evaluate the effect of infusion of exogenous prostaglandin E1 on (1) hepatic ATP levels and (2) restoration of hepatic ATP-dependent intracellular function. Rats were subjected to hemorrhagic shock, resuscitated, and then treated with either prostaglandin E1 or a saline placebo. Ten minutes after the completion of treatment, hepatic ATP levels were significantly higher in prostaglandin-treated animals (1.37 ± 0.43 μmol/g) than in animals receiving the placebo (0.70 ± 0.11 μmol/g). Creatine phosphate levels were also higher in the prostaglandin-treated group (1.59 ± 0.16 μmol/g) than in the placebo-treated group (0.89 ± 0.14 μmol/g). Lactate production ratios, an index of ATP-dependent membrane function, were near the theoretical normal of 100% in unshocked, untreated animals (95 ± 10%). They were significantly reduced (57 ± 10%) in animals receiving only placebo, but were not significantly different from unshocked animals in those receiving prostaglandin E1 following shock (91 ± 10%). It is concluded that prostaglandin infusion improves both hepatic high-energy phosphate levels and ATP-dependent intracellular function following hemorrhagic shock. This might be due to replenishing the purine base, selectively increasing hepatic blood flow, or both.

In a model of severe hemorrhagic shock in rats, blood culture findings became positive within 2 to 4 hours of shock. The organisms cultured were primarily gram-negative. To test the hypothesis that the gut was the source of the bacteria, E. coli labeled with carbon-14 oleic acid were fed to rats undergoing hemorrhagic shock. Their plasma was then assayed for carbon-14 activity. Seven of the 14 shocked animals demonstrated increased plasma carbon-14 activity during or after shock. The mortality rate was 100 percent 80 hours postshock, and all animals had E. coli on subsequent blood culture. The seven rats without increased plasma carbon-14 activity had a survival rate of 83 percent postshock. Sham-shocked animals did not exhibit plasma carbon-14 levels greater than the background levels. These data suggest that bacterial translocation occurs during hemorrhagic shock and that the gut is the source of the bacteremia seen during hemorrhagic shock.

The classic symptoms of hypovolemic shock have probably been recognized since prehistoric times. Clear, written descriptions did not emerge until the 19th century, and the syndrome implied impending, unpreventable death until the 20th century. We now have the tools for resuscitation of the large majority of patients in shock. When the shock syndrome is encountered in the field, away from the hospital and the emergency room, rapid transportation to these areas of more sophisticated diagnosis and treatment is indicated.

Previous investigations of a treated model of hemorrhagic shock in the rat indicated the frequent occurrence of bacteremia that appeared to derive from the gut. This paper determines the incidence of bacteremia and endotoxemia during the acute shock period and compares this with similar observations in humans in varying degrees of shock. Studies in 26 rats indicated that bacteremia and endotoxemia was present in 50% and 87%, respectively, by the end of 2 hours at a mean arterial pressure of 30 mmHg. Observations in 50 patients admitted to the trauma unit showed that positive bacterial blood cultures were present in 56% when the admission systolic blood pressure was 80 mmHg or less (p less than 0.01 compared with either of the other groups). Endotoxemia was noticed in two such patients. Direct access of bacteria and endotoxin to the blood stream may occur during hemorrhagic or traumatic shock and is the probable cause of subsequent sepsis in traumatized patients when no other source is apparent.

This paper reviews eighty patients dying of acute pancreatitis, fifty in a hospital population and thirty who died in the community without ever receiving medical care. Our findings suggest the following conclusions: Death in the hospital from acute pancreatitis is often associated with misdiagnosis. Such patients frequently have associated disease which obscures the primary diagnosis and enzyme levels which are either not elevated or elevated only moderately. When no medical therapy is received by patients, death occurs earlier in the course of the disease, often associated with edematous pancreatitis, and often in younger patients. Acute lesions of the liver are found in half of these patients and we have speculated as to whether this is a cause or a result of the acute pancreatitis. Finally, the different incidence of edematous, hemorrhagic, and suppurative pancreatitis in the two groups indicated that edematous pancreatitis is the earlier lesion and leads subsequently to hemorrhagic and suppurative pancreatitis.

Two cases of neuroma of the common bile duct (CBD) associated with jaundice and cholangitis both 15 years after cholecystectomy are presented. The surgical treatment, excision of the diseased CBD, followed by Roux-en-Y biliary drainage in one case and excision of the tumor with T-tube drainage in the other, was curative. A review of the world literature revealed 20 prior cases of CBD neuromas, 19 associated with jaundice. None was diagnosed prior to operation or autopsy. Mortality of treatment was 15% and all deaths were associated with a failure to excise the neuroma.

The hemodynamic and microcirculatory effects of prostaglandin E1 and methylprednisolone sodium succinate were compared in a standard canine shock model. Prostaglandin significantly increased cardiac output and decreased total peripheral resistance when compared to control animals while steroids did not. There was no significant effect upon heart rate or arterial pressure by either drug. Methylprednisolone sodium succinate significantly increased arterial pH at the conclusion of the experiment and showed directional improvement in venous lactate and proteolytic activity. Prostaglandin significantly increased length of survival compared to both steroid and control infusion. It is concluded that prostaglandin and steroid have different hemodynamic effects in shock, that steroid protects microcirculatory flow more efficiently and that the prolongation of survival seen with prostaglandin infusion is not entirely due to its hemodynamic or lysosomal stabilizing effects.

We have recently reported the rapid appearance of bacteria and endotoxin in the blood of rats and of trauma patients in the course of 30 minutes to 2 hours of hemorrhagic shock. The current study was designed to determine the effect of this bacteremia and endotoxemia on survival. Thirty-three conventional (C:group 1) and 36 germ-free (GF:group 2) Sprague Dawley rats were subjected to our previously described model of treated hemorrhagic shock. Survival in the GF group was significantly better than the C group at 24, 48, and 72 hours after shock. Endotoxin levels were elevated in 88% of C group during shock and in 28% of GF group. The gut of the GF animal contains endotoxin (26 ng/gm of stool) as does the sterile food supply (393 ng/gm of rat chow).

A shock preparation has been developed which produces the expected anaerobic metabolism in neonatal beagle puppies less than 7 days old. Lactic acid production was found to be significantly higher in shocked puppies operated upon under local anesthesia than when the same procedures were performed in shocked puppies under general endotracheal anesthesia. These findings suggest that general anesthesia may be safer in the very sick human neonate.

We have reviewed the clinical course and histologic findings in 84 patients with stage I and II squamous carcinoma of the mouth floor. We concluded that lesion thickness may offer a useful method for predicting the probability of cervical metastasis in node negative (N0) patients. Moreover, surface area of the lesion did not correlate with subsequent nodal disease, whereas thickness did. Elective node dissection appears to be strongly indicated in any patient with a N0 lesion measuring more than 1.5 mm in thickness.

The concept of irreversibility in shock was popularized by Wiggers (94) about two decades ago. He demonstrated that, if dogs are bled enough to create profound hypotension, early replacement of normal blood volume results in survival, while late replacement is followed by a gradual drop in blood pressure and death—despite post-treatment restoration of blood pressure to normal and a normal blood volume. Wiggers called this latter phase “normovolemic shock” and indicated that it was resistant to all modes of therapy then current. Some feel that this concept is of little use in describing clinical shock, stating (a) that human shock is rarely permitted to reach the levels used in canine experiments, (b) that no such clear-cut moment exists in clinical shock when irreversibility supervenes, and (c) that, in any case, the dog is an unacceptable model for human shock (64). However, the concept of irreversibility persists as a challenge to many investigators and appears to have outgrown the old connotations of the experimental model, reflecting instead the current state of the art. Thus, clinical shock which fails to respond to all the agents we command is irreversible.

Irreversibles an enigma in experimental animals and in man. Much work has been done in an effort to elucidate the pathophysiological changes which characterize the state of "irreversibility" so that specific therapy may be directed at these disturbances. Even though irreversible shock cannot be defined as precisely in man as in the dog, it seems likely that the basic metabolic consequences of prolonged shock are similar in both species. The differences in the pathological manifestations of shock between man and experimental animals seem related to differences in susceptibility of various organs to the hemodynamic changes of shock. Lillehei 1 has proposed a unified concept in which the stage of irreversibility, whether induced by hemorrhage, bacterial endotoxins, or myocardial failure, is characterized by loss of tone in precapillary arterial sphincters while postcapillary sphincters remain constricted. The result is a progressive loss of plasma from the vascular system, stagnant anoxia and congestion

The occurrence of high fever in an otherwise well child, a day or two after operation, leads the experienced surgeon to throw back the sheets and look for a saphenous phlebitis at the site of a cut-down. The child is usually not particularly ill, although there is generally a visible erythema, tenderness, induration along the course of the vein, and frequently edema of the leg. Blood cultures made by ordinary methods are generally sterile. The condition responds at once to withdrawal of the intravenous cannula, polyethylene catheter, or indwelling needle and local application of hot compresses. The plastic indwelling catheters have become particularly popular and have led to the more frequent use of continuous intravenous drips. A number of reports have appeared listing the hazards and complications which result from use of this technique.1Septic thrombophlebitis is probably the most serious complication and has led to bacteremia and septicemia

In the course of metabolic studies in dogs following nephrectomy and ureteral ligation, it was noted that the chloride content of the excreta was often quite high. Since the excreta in this situation is almost entirely vomitus, we were attracted to a consideration of the components of gastric juice in uremia. The available data is sketchy in this regard. Peters 1 noted that the gastric aspirate in patients with chronic uremia was low in both chloride and titratable acidity. Schreiner and Maher 3 in an extensive review of the subject of the gastrointestinal symptoms of uremia do not refer to any studies of the acidity or electrolyte content of gastric juice under these circumstances. They take note of the high incidence of uremic gastritis, heart burn, vomiting, and gastric bleeding in uremia, and are inclined to favor the high concentration of ammonia which develops in the intestinal tract as the