Association between heart rate variability recorded on postoperative day 1 and length of stay in abdominal aortic surgery patients.

OBJECTIVE: To determine whether heart rate variability (HRV) measured in the surgical intensive care unit (ICU) on the first postoperative day predicts clinical outcome in patients undergoing abdominal aortic surgery. DESIGN: Prospective study. SETTING: Eighteen-bed surgical ICU of a 1,442-bed university hospital. PATIENTS: One hundred and six patients admitted to the ICU after abdominal aortic surgery. MEASUREMENTS AND MAIN RESULTS: Twenty-four-hour Holter recordings were analyzed for standard time and frequency domain indices and one nonlinear index (slope) of HRV. Clinical and demographic data were collected from medical records. Patients were dichotomized into short (< or = 7 days) and long (> 7 days) length of stay (LOS) by median split. Patients with long LOS had increased heart rates and decreased short- and intermediate-term HRV but no difference in overall HRV, which primarily reflects circadian rhythm. Independent predictors of LOS were increased age, insulin-dependent diabetes, and decreased HRV. CONCLUSIONS: Increased heart rates and decreased intermediate-term HRV indices measured on postoperative day 1 were independent predictors of complicated recovery. The strongest HRV predictors of outcome were natural logarithm very-low-frequency power measured over 24 hrs and during the daytime. Results support the potential use of HRV for the prediction of postsurgical resource utilization.

Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans.

Patients with sepsis have impaired host defenses that contribute to the lethality of the disorder. Recent work implicates lymphocyte apoptosis as a potential factor in the immunosuppression of sepsis. If lymphocyte apoptosis is an important mechanism, specific subsets of lymphocytes may be more vulnerable. A prospective study of lymphocyte cell typing and apoptosis was conducted in spleens from 27 patients with sepsis and 25 patients with trauma. Spleens from 16 critically ill nonseptic (3 prospective and 13 retrospective) patients were also evaluated. Immunohistochemical staining showed a caspase-9-mediated profound progressive loss of B and CD4 T helper cells in sepsis. Interestingly, sepsis did not decrease CD8 T or NK cells. Although there was no overall effect on lymphocytes from critically ill nonseptic patients (considered as a group), certain individual patients did exhibit significant loss of B and CD4 T cells. The loss of B and CD4 T cells in sepsis is especially significant because it occurs during life-threatening infection, a state in which massive lymphocyte clonal expansion should exist. Mitochondria-dependent lymphocyte apoptosis may contribute to the immunosuppression in sepsis by decreasing the number of immune effector cells. Similar loss of lymphocytes may be occurring in critically ill patients with other disorders.

A prospective, randomized study comparing percutaneous with surgical tracheostomy in critically ill patients.

OBJECTIVE: To determine the relative cost-effectiveness of percutaneous dilational tracheostomy (PDT) and surgical tracheostomy (ST) in critically ill patients. DESIGN: Prospective randomized study. SETTING: Medical, surgical, and coronary intensive care units at Barnes-Jewish Hospital, a tertiary care medical center. PATIENTS: Eighty critically ill mechanically ventilated patients requiring elective tracheostomy. INTERVENTIONS: Randomization to either PDT performed in the intensive care unit or ST performed in the operating room. MEASUREMENTS AND MAIN RESULTS: Treatment groups were well matched with respect to age (PDT, 65.44 +/- 2.82 [mean +/- se] years; ST, 61.4 +/- 2.89 years, p = Ns), gender (PDT, 45% males; ST, 47.5% males, p = NS), severity of illness (Acute Physiology and Chronic Health Evaluation II score: PDT, 16.87 +/- 0.84; ST, 17.88 +/- 0.92, p = NS), and principle diagnosis. PDT was performed more quickly (PDT, 20.1 +/- 2.0 mins; ST, 41.7 +/- 3.9 mins, p < .0001) and was associated with lower patient charges than ST (total patient charges: PDT, 1,569 dollars +/- 157 dollars vs. ST, 3,172 dollars +/- 114 dollars; equipment/supply charges: PDT, 688 dollars +/- 103 dollars vs. ST, 1,526 dollars +/- 87 dollars; professional charges: PDT, 880 dollars +/- 54 dollars vs. ST, 1,647 dollars +/- 50 dollars; p < .0001 for all). There were no differences in days intubated before tracheostomy (PDT, 12.7 +/- 1.1 days; ST, 15.6 +/- 1.9, p = .20), intensive care unit length of stay (PDT, 24.5 +/- 2.5 days; ST, 28.5 +/- 3.1 days, p = .33), or hospital length of stay (PDT 49.7 +/- 4.2 days; ST, 43.7 +/- 3.5 days, p = .28) when we compared these two techniques. CONCLUSIONS: PDT is a cost-effective alternative to ST. The reduction in patient charges associated with PDT in this study resulted from the procedure being performed in the intensive care unit, thus eliminating the need for operating room facilities and personnel. PDT may become the procedure of choice for electively establishing tracheostomy in the appropriately selected patient who requires long-term mechanical ventilation.

Rapid onset of intestinal epithelial and lymphocyte apoptotic cell death in patients with trauma and shock.

OBJECTIVE: Apoptosis is a cellular suicide program that can be activated by cell injury or stress. Although a number of laboratory studies have shown that ischemia/reperfusion injury can induce apoptosis, few clinical studies have been performed. The purpose of this study was to determine whether apoptosis is a major mechanism of cell death in intestinal epithelial cells and lymphocytes in patients who sustained trauma, shock, and ischemia/ reperfusion injury. DESIGN: Intestinal tissues were obtained intraoperatively from 10 patients with acute traumatic injuries as a result of motor vehicle collisions or gun shot wounds. A control population consisted of six patients who underwent elective bowel resections. Apoptosis was evaluated by conventional light microscopy, laser scanning confocal microscopy using the nuclear staining dye Hoechst 33342, immunohistochemical staining for active caspase-3, and immunohistochemical staining for cytokeratin 18. SETTING: Academic medical center. PATIENTS: Patients with trauma or elective bowel resections. MEASUREMENTS AND MAIN RESULTS: Extensive focal crypt epithelial and lymphocyte apoptosis were demonstrated by multiple methods of examination in the majority of trauma patients. Trauma patients having the highest injury severity score tended to have the most severe apoptosis. Repeat intestinal samples obtained from two of the trauma patients who had a high degree of apoptosis on initial evaluation were negative for apoptosis at the time of the second operation. Tissue lymphocyte apoptosis was associated with a markedly decreased circulating lymphocyte count in 9 of 10 trauma patients. CONCLUSIONS: Focal apoptosis of intestinal epithelial and lymphoid tissues occurs extremely rapidly after injury. Apoptotic loss of intestinal epithelial cells may compromise bowel wall integrity and be a mechanism for bacterial or endotoxin translocation into the systemic circulation. Apoptosis of lymphocytes may impair immunologic defenses and predispose to infection.

Common and external iliac artery injuries associated with pelvic fractures.

BACKGROUND: Common and external iliac artery injuries associated with pelvic fractures are uncommon. The diagnosis of such injuries is based on clinical findings and confirmed by arteriography. DESIGN: Retrospective chart review. SETTING: University Level I trauma center. PATIENTS: Five men and three women, aged seventeen to seventy-six years, with injuries to the common and external iliac arteries associated with pelvic fractures. RESULTS: All patients sustained complex pelvic fractures associated with multiple blunt injuries. Five injuries occurred on the right side. Two patients had an associated right vertical shear pelvic fracture. In five patients, vascular injury was diagnosed in the first six hours after admission. One patient presented with an aneurysm of the right common iliac artery two months after his initial injury. All patients underwent surgical repair with an interposition graft, which failed in two patients, who underwent vascular reconstruction ten hours after the injury. One patient died of associated injuries. CONCLUSIONS: Arterial hyperextension with intimal damage seems to be the most likely cause of this injury. Ideally, an extraperitoneal approach should be attempted to minimize blood losses and, due to the size of the iliac vessels, an interposition graft should be used for reconstruction.

Interventional techniques are useful adjuncts in nonoperative management of hepatic injuries.

BACKGROUND: Nonoperative management has become the standard of care for hemodynamically stable patients with complex liver trauma. The benefits of such treatment may be obviated, though, by complications such as arteriovenous fistulas, bile leaks, intrahepatic or perihepatic abscesses, and abnormal communications between the vascular system and the biliary tree (hemobilia and bilhemia). METHODS: We reviewed the hospital charts of 135 patients with blunt liver trauma who were treated nonoperatively between July 1995 and December 1997. RESULTS: Thirty-two patients (24%) developed complications that required additional interventional treatment. Procedures less invasive than celiotomy were often performed, including arteriography and selective embolization in 12 patients (37%), computed tomography-guided drainage of infected collections in 10 patients (31%), endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy and biliary endostenting in 8 patients (25%), and laparoscopy in 2 patients (7%). Overall, nonoperative interventional procedures were used successfully to treat these complications in 27 patients (85%). CONCLUSION: In hemodynamically stable patients with blunt liver trauma, nonoperative management is the current treatment of choice. In patients with severe liver injuries, however, complications are common. Most untoward outcomes can be successfully managed nonoperatively using alternative therapeutic options. Early use of these interventional procedures is advocated in the initial management of the complications of severe blunt liver trauma.

Percutaneous dilational tracheostomy for airway control.

BACKGROUND: Endoscopic percutaneous dilational tracheostomy (PDT) is a good alternative to obtain safe and secure long-term airway control, and is associated with minimal morbidity and mortality. STUDY DESIGN: During a 14-month period, we prospectively studied 35 intensive care unit (ICU) trauma patients who underwent early PDT for the sole purpose of obtaining long-term airway control. All patients were determined to need a tracheostomy owing to extubation inability, need to maintain a patent airway, or need for continuous airway access for management of secretions. RESULTS: All patients had sustained multiple injuries with an average Injury Severity Score (ISS) of 29. The time from ICU admission to placement of the PDT was 8 +/- 5 days. The mean Glasgow Coma Scale at the time of the PDT was 10 (range 4 to 15), and 11 patients (31%) had an intracranial pressure device in place. The procedure was completed with bronchoscopic guidance in 33 patients, and in 2 it was converted to surgical tracheostomy (ST). There were no significant complications associated with the placement of the PDT. Two deaths were documented, neither related to the PDT placement. Compared with standard ST, charges were reduced by $1,750. CONCLUSIONS: Bedside endoscopic PDT for selected critically ill trauma patients is justified as a safe and effective alternative to ST. The low incidence of complications in PDT suggests that it can be done safely at bedside in the ICU.

The impact of previous abdominal surgery on outcome following laparoscopic cholecystectomy.

The first 1000 patients undergoing laparoscopic cholecystectomy (LC) at our institution were reviewed to investigate the impact of previous abdominal surgery on LC. The 454 patients having no previous abdominal surgery (NS) were compared to the 541 patients who had previous surgery (PS). PS patients were older, more likely to be female, and had a higher ASA risk category. PS patients had a higher incidence of wound infection, but in all other parameters of outcome, including operative duration and completion, length of hospitalization, and morbidity, there were no significant differences between PS and NS. When PS patients with previous upper abdominal surgery (PUAS, n = 59) were separately compared to the remainder of the entire patient group (NUAS, n = 936), the PUAS group was found to be older, to be more likely to be male, and to have a higher ASA risk category. PUAS patients had a longer postoperative hospitalization, and an increased incidence of intraoperative, postoperative, and total complications, readmissions to the hospital, and unrelated deaths. We conclude previous lower abdominal surgery has little impact on the outcome of patients undergoing LC while previous upper abdominal surgery is associated with increased morbidity.

Laparoscopic versus traditional appendectomy for suspected appendicitis.

We compared the results of concurrently performed laparoscopic versus open appendectomy as treatments for suspected acute appendicitis. The 68 laparoscopic procedures resulted in 62 appendectomies, 47 by the laparoscopic (LA) technique and 15 by the open (LO) technique. Another 54 patients underwent open appendectomy (OA). Significantly more females underwent laparoscopy (LA and LO: 52% versus OA: 33%, p = 0.047). Operative duration was shortest for OA (81 +/- 3 minutes), which was shorter than for LO (108 +/- 7 minutes), but not different than LA (86 +/- 6 minutes). The postoperative length of stay was not different for LA (3.5 +/- 0.5 days) compared with OA (5.9 +/- 1.6 days) or LO (4.8 +/- 1.3 days). One death occurred in the OA group. Wound complication rates were not significantly different for LA (4.3%) compared with OA (9.4%) and LO (13.3%). Overall complication rates were lower for LA (10.6%) and OA (18.9%) compared with LO (46.7%, p < 0.01). Median hospital cost for LO ($10,425) was higher (p < 0.02) than for either LA ($5,899) or OA ($5,220). When appendicitis was not present, definitive confirmation of pathology was achieved in 9 of 18 patients undergoing LA versus 4 of 14 patients having OA (p = not significant). We conclude that when laparoscopy and laparoscopic appendectomy can be performed, the procedure is safe and produces results comparable with those of open appendectomy without significant overall cost differences.

Pancreas cancer resection outcome in American University centers in 1989-1990.

BACKGROUND: Series of patients with pancreas cancer from single high-volume institutions or surgeons have demonstrated improvements in morbidity and mortality of pancreatic resection in recent decades. The experience of these single institutions or surgeons may not, however, reflect the results achieved by a cross-section of surgeons or hospitals. This article examines the resection outcome for a large unselected group of university hospitals and surgeons. METHODS: Pancreas cancer resection morbidity and mortality were examined using a multi-institution data base of discharge coding data from 26 American university hospitals. The data were analyzed for relationships of morbidity and mortality with the type of resection, patient age, hospital volume, and individual surgeon case load. RESULTS: Two hundred twenty-three resections were performed in 1989-1990 (pancreaticoduodenectomy, 168 patients; total pancreatectomy, 11; distal pancreatectomy, 30; and islet tumor resection, 14). The mortality rate was 6% (13 of 223) with major complications in 21%. Patient age did not correlate with complications or death. The surgeon case load ranged from 1-15 cases (median, 1) over the 2-year period. The mortality rate did not correlate with the case load. Surgeons performing one to three resections had significantly more complications than those performing four or more resections (P = 0.011). CONCLUSIONS: Pancreas resection is performed by an unselected cross-section of surgeons in American university centers with acceptable morbidity and mortality rates.

Meal-stimulated absorption of water and electrolytes in canine jejunum.

After a meal, the absorption of water and electrolytes from the jejunal lumen increases. This meal-induced jejunal absorption occurs in jejunal segments out of normal gastrointestinal continuity. The experimental model used 25-cm proximal jejunal Thiry-Vella loops in awake dogs (n = 72 observations) to evaluate the mechanisms involved in meal-induced jejunal absorption, seeking to define the source or sources of the proabsorptive signal. Specifically, we evaluated the jejunal absorptive response to a standard meal, a standard meal plus cholinergic blockage using atropine, a sham-fed meal, a gavage-fed meal, and gastric distension with balloon and gavage water. Both the standard meal and the gavage-fed meal induced a prompt, sustained, and significant (P less than 0.0001) increase in the absorption of H2O, Na+, and Cl-. Atropine significantly reduced the magnitude of the postmeal absorptive response (P less than 0.05) compared with the standard meal alone. The sham-fed meal, gastric balloon distension, and gavage water did not alter jejunal absorption. Vagal nerve integrity after cervical esophageal manipulation was verified by gastric acid output and gastrin response to stimuli. These data support a role for cholinergic modulation of meal-stimulated jejunal absorption via a cephalic-phase-independent and gastric-distension-independent mechanism.

The proabsorptive effect of D-ala2-metenkephalinamide is mediated by naloxone-sensitive opiate receptors in the isolated perfused ileum.

Methionine-enkephalin is an endogenous opiate pentapeptide, originally isolated in the brain, that exists within enteric plexuses and enterocytes. The purpose of this study was to delineate the effects of the opiate agonist methionine-enkephalin on intestinal water and electrolyte transport, with the stable analog D-ala2-metenkephalinamide (m-ENK). Ileal segments from New Zealand white rabbits (n = 39) were harvested and vascularly and luminally perfused ex vivo. Net fluxes of H2O, Na+, and Cl- were calculated for three 20-minute periods: basal, drug infusion, and recovery. Six groups were studied: (1) control, (2-4) m-ENK at three doses, (5) naloxone, and (6) naloxone plus m-ENK. Oxygen consumption and arterial perfusion pressure were assessed as measures of metabolic activity and viability. The control and naloxone groups had no changes in the fluxes of water and electrolytes. Significant proabsorptive effects were demonstrated for the fluxes of H2O, Na+, and Cl- at increasing doses of m-ENK (p less than 0.05). Naloxone completely prevented m-ENK-induced absorption. These results with exogenous m-ENK suggest that endogenous methionine-enkephalin, serving as an enteric neurotransmitter and acting through naloxone-sensitive opiate receptors, may function as a physiologic modulator of intestinal water and electrolyte absorption.

The effect of pancreatic polypeptide infusion on glucose tolerance and insulin response in longitudinally studied pancreatitis-induced diabetes.

Glucose intolerance is often associated with pancreatitis. Pancreatitis-induced diabetes represents a different clinical syndrome than type I and type II diabetes mellitus. Patients with pancreatitis-induced diabetes may be extremely sensitive to exogenous insulin, rarely develop ketoacidosis, and rarely exhibit classic diabetic complications, such as retinopathy, nephropathy, or accelerated vasculopathy. Pancreatic polypeptide (PP) deficiency has been implicated in the defect of glucose homeostasis found after pancreatitis. This study evaluated intravenous and oral glucose tolerance and insulin response to glucose loading, in the setting of pancreatitis, with and without short-term PP replacement. Dogs (n = 7) underwent pancreatic duct ligation (PDL) and were studied with and without PP infusion (2 micrograms/kg/hr) before PDL and at 1 week, 6 weeks, and 4 months after PDL by means of intravenous and oral glucose tolerance tests. Basal and bombesin-stimulated PP levels at 4 months after PDL were subnormal, verifying PP deficiency in these animals with pancreatitis. PP levels during PP infusion reproduced normal postcibal levels, averaging 897 +/- 40 pg/ml. Glucose tolerance, expressed as the glucose decay constant for the intravenous glucose tolerance tests and as the integrated glucose response for the oral glucose tolerance tests, deteriorated over time and was not improved by acute PP replacement. The integrated insulin response to glucose was not affected by PP. The acute infusion of PP at a dose that reproduces normal postprandial PP levels fails to improve glucose tolerance or augment insulin release in this model of pancreatitis-induced diabetes.

Pancreatic structure and glucose tolerance in a longitudinal study of experimental pancreatitis-induced diabetes.

Chronic pancreatitis is associated with glucose intolerance and resultant pancreatogenic diabetes. Using the canine pancreatic duct-ligated model of pancreatitis, we serially evaluated pancreatic histology and electron microscopy, tolerance to intravenous and oral glucose, and insulin response to glucose loading. Pancreatic duct ligation caused microscopic evidence of acute pancreatitis at 1 week, progressing to acinar loss and fibrosis consistent with chronic pancreatitis at time periods up to 6 months. The islets of Langerhans showed degranulation early and appeared to be structurally preserved late. Calculated K values indicated a progressive significant deterioration in intravenous glucose tolerance, falling significantly from 3.46 +/- 0.23 basally to 1.51 +/- 0.17 at 6 months after duct ligation (p less than 0.0001). Oral glucose tolerance deteriorated significantly, with the integrated glucose response rising from 23.7 +/- 1.2 g/dl.minute basally to 32.3 +/- 2.8 g/dl.minute at 6 months after duct ligation (p less than 0.05). Integrated insulin response to both intravenous and oral glucose deteriorated with pancreatitis. Pancreatitis-induced glucose intolerance is a consistent feature of this duct-ligated model. Glucose intolerance stabilizes between 4 and 6 months after duct ligation and is associated with pancreatic acinar fibrosis and pancreatic endocrine structural preservation. While the mechanism of altered glucose tolerance may involve mechanical, neural, humoral, or vascular events, our data clearly support the conclusion that pancreatic ductal stenosis with resultant pancreatic fibrosis and chronic pancreatitis is associated with abnormal islet responsiveness leading to circulating insulin deficiency and glucose intolerance, despite histologic and ultrastructural evidence of intact islets of Langerhans.

Postreceptor mechanisms of small-bowel water and electrolyte transport.

Neurohumoral agents modulate intestinal transport by interactions with cell membrane receptors. Intracellular second messenger systems implicated in mediation of membrane receptor regulation of cellular events include the phosphoinositide and adenylate cyclase systems. In this study we have investigated the effects of direct postreceptor activation of key components of these systems on intestinal water and electrolyte transport. Rabbit ileal segments (n = 35) were arterially perfused ex vivo with an oxygenated sanguineous solution. The lumen was perfused with an isotonic solution containing 14C-polyethylene glycol as a nonabsorbable marker. Net fluxes of H2O, Na+, and Cl- in six experimental groups were calculated for three 20-minute periods: basal, drug infusion, and recovery. The control group had no drug infusion. Two phorbol esters--phorbol 12, 13-diacetate (PDA; 10(-5) mol), and phorbol 12, 13-dibutyrate (PDB; 10(-5) mol)--were used to activate protein kinase C, an important component of the phosphoinositide system. The inactive 4 alpha-phorbol 12, 13-didecanoate (PDD; 10(-5) mol) served as a drug-infused control. Forskolin at two doses (FOR; 10(-5) mol and 10(-6) mol) was used to activate adenylate cyclase. The control and PDD groups had no changes in the flux of water and electrolytes. Both PDA and PDB had proabsorptive effects, with the more lipophilic and potent phorbol ester (PDB) having a more pronounced, significant effect (p less than 0.05). FOR caused significant secretion of H2O, Na+, and Cl- in a dose-dependent fashion (p less than 0.05). These results indicate that direct protein kinase C activation causes a proabsorptive effect and that direct activation of adenylate cyclase causes a secretory effect in the isolated small bowel. The activation status of these second messenger systems has a major influence on the transport state of the intestine.

Luminal adrenergic agents modulate intestinal transport.

Intestinal transport is controlled by luminal solutes, neural pathways, and paracrine or humoral agents. The current study investigated the effect of luminally administered adrenergic agents on the intestinal transport of water and electrolytes. Dogs with 25-cm jejunal Thiry-Vella loops were studied. The loops were luminally perfused with an isotonic solution containing [14C]PEG, and the fluxes of H2O, Na+, and Cl- were calculated. Each experiment consisted of three 1-hr periods: basal, luminal agent infusion, and recovery. Luminal adrenergic agents did not alter heart rate. Norepinephrine (alpha 1 greater than alpha 2 and beta adrenergic agonist) and phenylephrine (alpha 1 adrenergic agonist) caused significant absorption of water and sodium. Clonidine (alpha 2 adrenergic agonist) and isoproterenol (beta adrenergic agonist) caused significant secretion of water, sodium, and chloride. Luminally administered adrenergic agents can influence small intestinal water and electrolyte transport. Alpha 1 agonists have a proabsorptive effect, while alpha 2 and beta agonists have a secretory effect. Luminally administered proabsorptive adrenergic agents may prove useful in pathologic secretory states such as diabetic diarrhea, small bowel transplantation, or diarrhea-associated endocrinopathies.