Bundle-branch block as a risk factor in noncardiac surgery.

BACKGROUND: Despite extensive data examining perioperative risk in patients with coronary artery disease, little attention has been devoted to the implications of conduction system abnormalities. OBJECTIVE: To define the clinical significance of bundle-branch block (BBB) as a perioperative risk factor. METHODS: Retrospective, cohort-controlled study of all noncardiac, nonophthalmologic, adult patients with BBB seen in our preoperative evaluation center. Medical charts were reviewed for data regarding cardiovascular disease, surgical procedure, type of anesthesia, intravascular monitoring, and perioperative complications. RESULTS: Bundle-branch block was present in 455 patients. Right BBB (RBBB) was more common than left BBB (LBBB) (73.8% vs 26.2%). Three patients with LBBB and 1 patient with RBBB died; 1 patient had a supraventricular tachyarrhythmia. Three of the 4 deaths were sepsis related. There were 2 (0.4%) deaths in the control group. There was no difference in mortality between BBB and control groups (P = .32). Subgroup analysis suggested an increased risk for death in patients with LBBB vs controls (P = .06; odds ratio, 6.0; 95% confidence interval, 1.2-100.0) and vs RBBB (P = .06; odds ratio, 8.7; 95% confidence interval, 1.2-100.0). CONCLUSIONS: The presence of BBB is not associated with a high incidence of postoperative cardiac complications. Perioperative mortality is not increased in patients with RBBB and not directly attributable to cardiac complications in patients with LBBB. These data suggest that the presence of BBB does not significantly increase the likelihood of cardiac complications following surgery, but that patients with LBBB may not tolerate the stress of perioperative noncardiac complications.

Weight loss is not associated with hyperleptinemia in humans with pancreatic cancer.

Pathological weight loss is a feature of many diseases and contributes to mortality and morbidity. Although cytokines have been implicated in some models of pathological weight loss, little is known about cellular mechanisms responsible for cachexia in patients with cancer. Leptin is a fat cell product that acts centrally to reduce appetite and decrease metabolism. Leptin synthesis is stimulated by cytokines, and circulating levels of cytokines are elevated in some cancer patients. We hypothesized that cytokine-induced hyperleptinemia contributes to pathological weight loss in patients with pancreatic cancer. To evaluate this hypothesis, fasting serum leptin concentrations were measured in 64 patients undergoing surgery for pancreatic cancer. Preoperative interviews were used to assess body weight and appetite history. Thirty of 64 pancreatic cancer patients had cachexia (weight loss of >10% over the 6 months before surgery). Self-reported loss of appetite was associated with the presence of cachexia. Leptin concentrations, when corrected for body mass index, were lower than levels reported in healthy humans. Six patients had leptin levels more than 2 times those predicted by body mass index. There was no association between patients with increased leptin concentration and weight loss or anorexia. We conclude that a reduced appetite contributes to weight loss in patients with pancreatic cancer. High plasma leptin levels, however, do not appear to contribute to cachexia in these patients.

Role of gamma-aminobutyric acid in antipanic drug efficacy.

All effective pharmacologic agents used to treat panic disorder augment gamma-aminobutyric acid (GABA) transmission. Anxiolytics and antidepressants that lack GABA activity are not effective in panic disorder. To test the hypothesis that GABA activity is a component of antipanic drug efficacy, the authors treated nine medication-free panic disorder subjects with oral baclofen (30 mg/day for 4 weeks) in a double-blind, placebo-controlled crossover trial. Baclofen, a selective GABA agonist, was significantly more effective than placebo in reducing the number of panic attacks and scores on the Hamilton anxiety scale, Zung scale, and Katz-R nervousness subscale. The authors discuss possible mechanisms of antipanic drug efficacy.

Substance abuse-related admissions to adult intensive care.

The frequency of adult surgical and medical intensive care unit (ICU) admissions related to substance abuse was determined at a large community, trauma, and tertiary referral hospital. Of 435 ICU admissions, 14 percent (95 percent confidence interval [CI], 5 to 23 percent) were tobacco related generating 16 percent of costs, 9 percent (95 percent CI, 0 to 18 percent) were alcohol related generating 13 percent of costs, and 5 percent (95 percent CI, 0 to 14 percent) were illicit drug related generating 10 percent of costs. In all, 28 percent (95 percent CI, 20 to 36 percent) of ICU admissions generating 39 percent of costs were substance abuse related. Substance abuse-related admissions were significantly longer and more costly than admissions not related to substance abuse (4.2 days vs 2.8 days, p = 0.004; $9,610 vs $5,890, p = 0.001). Frequency of substance abuse-related admission was linked with the patient's insurance status (Medicare, private insurance, uninsured). In the uninsured group, 44 percent of admissions were substance abuse related (95 percent CI, 35 to 52 percent), significantly higher than in the private insurance and Medicare groups, and generating 61 percent of all ICU costs in the uninsured group. Large fractions of adult ICU admissions and costs are substance abuse related, particularly in uninsured patients.

Atypical beta-adrenoceptor in bovine adrenal medulla.

Bovine adrenal medullary membranes were incubated with [125I]cyanopindolol to assess beta-adrenoceptor binding. Binding was saturable and specific; a single low affinity site (Kd = 750 pM) was identified. [125I]Cyanopindolol binding was displaced by micromolar concentrations of classic beta-adrenoceptor antagonists and by sodium-4-[-2-[2-hydroxy-2-(-3-chloro-phenyl) ethylamino] propyl] phenoxyacetate. These data are similar to reported binding of beta 3-adrenoceptors and may explain beta-adrenoceptor agonist modulation of chromaffin cell degranulation in this catecholamine rich environment.

Beta-3 adrenoceptor (beta-3AR) expression in leptin treated OB/OB mice.

Leptin-deficient Ob/Ob mice are hypometabolic and have reduced fat cell expression of beta-3 adrenoceptors (ARs). To determine whether leptin repletion restores beta-3 AR number, C57BL/6J Ob/Ob mice were given exogenous leptin (5 mg/kg I.P. daily) for 21 days. Leptin administration reduced body weight from 43.1+/-3.7 to 34.1+/-3.7 g in Ob/Ob animals but had no effect on weight in wildtype animals. Body weight increased by 12% in Ob/Ob mice receiving saline. Beta-3 AR mRNA concentrations were markedly reduced in Ob/Ob animals at baseline. Leptin increased beta-3 AR mRNA to control levels in Ob/Ob mice, but had no effect in wildtype animals. Adipocyte leptin mRNA was increased by 400% in Ob/Ob mice and did not suppress with exogenous leptin administration, suggesting no direct feedback regulation of leptin synthesis. We speculate that restoration of beta-3 AR expression by repleting leptin may be important in correcting hypometabolism in Ob/Ob animals.

ICU telemedicine. Organization and communication.

Telemedicine offers off-site physicians the ability to care for patients by providing them with audio-video links and access to relevant clinical data. Traditionally, this care modality has been used to overcome geographic barriers by bringing needed expertise to patients in remote locations. The same technology can be used to bring intensivist expertise to ICU patients. A recent clinical trial has confirmed the efficacy of remote ICU care, with decreases in mortality, complications, and costs that are analogous to those observed with on-site intensivists. If a single, intensivist-led care team can provide round-the-clock, proactive care to patients in multiple ICUs simultaneously, this care modality can be used to overcome current deficiencies in ICU care related to inadequate intensivist availability.

The stress response of critical illness.

The integrated stress response to tissue trauma is crucial for the maintenance of homeostasis. An exaggerated or prolonged response may be detrimental in compromised patients. Knowledge of the involved afferent pathways will suggest therapeutic interventions that may modulate the intensity of the stress response. Described are these concepts as they relate to perioperative medicine.

Adrenal insufficiency--an unusual cause of shock in postoperative patients.

OBJECTIVE: To remind physicians that adrenal insufficiency can cause postoperative shock and that the manifestations are difficult to distinguish from those of sepsis. METHODS: We present detailed case reports of three patients who had hyperdynamic shock in the surgical intensive-care unit and describe their response to the cosyntropin stimulation test. RESULTS: All three patients were diagnosed as having adrenal insufficiency with use of the cosyntropin stimulation test. Two of the three patients rapidly recovered; however, because of delay in the diagnosis of adrenal insufficiency, the third patient succumbed to multisystem organ failure. CONCLUSION: The cases presented highlight the need to exclude adrenal insufficiency as a possible cause of hyperdynamic circulatory shock, particularly when no clear-cut diagnosis exists. Early recognition of adrenal insufficiency is important and can result in reversal of shock and prevention of death. Adrenal insufficiency can be diagnosed through screening random cortisol levels and by use of the cosyntropin stimulation test. Patients in addisonian crisis often respond to the first dose of glucocorticoid with dramatic improvement in blood pressure and systemic vascular resistance. Administration of glucocorticoid can thus lead to improved organ perfusion and recovery of organ function. Delays in diagnosis and treatment of acute hypoadrenalism can have a fatal outcome.

Nicardipine versus nitroprusside for breakthrough hypertension following carotid endarterectomy.

STUDY OBJECTIVE: To evaluate the effectiveness of nicardipine and nitroprusside for breakthrough hypertension following carotid endarterectomy. DESIGN: Prospective, randomized, double-blind, controlled effectiveness trial. SETTING: University-based surgical intensive care unit. PATIENTS: 60 ASA physical status I, II, III, and IV patients experiencing breakthrough hypertension at the time of admission to the intensive care unit (ICU). INTERVENTIONS: Patients received either nicardipine (n = 29) and placebo or nitroprusside (n = 31) and placebo for up to 6 hours postoperatively. Loading doses of nicardipine were provided, but placebo was used as a load for patients randomized to nitroprusside. MEASUREMENTS AND MAIN RESULTS: Rapidity and variability of blood pressure (BP) control were assessed. During the first 10 minutes, 83% of nicardipine patients compared to 23% of nitroprusside-treated patients, achieved BP control (p < 0.01). Following initial control, 12 nicardipine- and 24 nitroprusside-treated patients required additional titration of their infusions to maintain blood pressure within the targeted range (p < 0.05). No patient suffered a stroke, myocardial infarction, or was returned to the operating room (OR) for bleeding. CONCLUSIONS: Nicardipine administration produced more rapid BP control, most likely related to the administration of a loading dose. In addition to more rapid control, nicardipine-treated patients had less variability in BP and required significantly fewer additional interventions. Although no patient suffered a major event during this study, this study was not powered sufficiently to assess safety.

Distal biceps tendon ruptures: a historical perspective and current concepts.

Distal biceps tendon rupture is a relatively rare injury most commonly seen in the dominant extremity of men between 40 and 60 years of age. It occurs when an eccentric extension force is applied to a contracting biceps muscle. The hallmark finding is a palpable defect in the distal biceps, which is accentuated by elbow flexion. Radiographic evaluation is usually not necessary. Acute surgical repair is advocated for optimal return of function by either a one-incision or a modified two-incision muscle-splitting technique. The arm is protected for 6 to 8 eight weeks after surgery. Unrestricted range of motion and gentle strengthening may begin after the 6 - 8 week protection period. Return to unrestricted activity is usually allowed by 5 months after surgery.

Cervical spine injuries in football.

The game of football, as it is played today, poses serious risk of injury for players of all ages. Injury may occur to any structure of the spinal column, including its bony, ligamentous and soft tissue components. The majority of cervical spine injuries occurring in football are self limited, and a full recovery can be expected. While these injuries are relatively uncommon, cervical spine injuries represent a significant proportion of athletic injuries that can produce permanent disability. The low incidence of cervical spine injuries has lead to a lack of emergency management experience of on-site medical staff. This paper will review the numerous injuries sustained by the cervical spine in football players and provide insights into prevention and guidelines for return to play.

The role of stress hormones in perioperative myocardial ischemia.

In this chapter I have tried to illustrate how trauma-induced changes in plasma catecholamines and other stress hormones can result in physiological alterations that may in turn increase the likelihood of developing myocardial ischemia. Data have been presented about potential mechanisms by which these hormones can lead to the development of ischemia, although additional work is required in this area. Among the strategies for modulating the stress response to surgery, the use of axial narcotics and perioperative administration of alpha 2-agonists can be easily instituted in most institutions. Additional studies are needed to determine whether these techniques reduce the incidence of perioperative ischemic complications. Because these interventions are labor intensive and therefore costly, further work is required to identify which subsets of patients may benefit from such aggressive management.

Regulation of adrenal medullary and cortical blood flow.

Before 1986, little was known concerning regulation of blood flow to adrenal medulla and cortex. With the introduction of a radiolabeled microsphere methodology, which permitted independent measurement of blood flow to the two regions, it became apparent that medulla and cortex regulate blood flow independently and that both regions receive levels of blood flow considerably in excess of that required for nutrient delivery. It is likely that abundant blood flow serves to speed entry of adrenal secretory products into the systemic circulation. Coupling of blood flow with secretion is particularly apparent in medulla, where severalfold increases in blood flow occur during catecholamine secretion elicited by hemorrhage, hypoxia, and splanchnic nerve stimulation. Both catecholamine secretion and medullary vasodilation are neurally mediated. The two responses can be pharmacologically dissociated, suggesting possible direct innervation of adrenal vessels. However, morphological confirmation of vascular innervation is not available, and effects of released chromaffin cell products on adjacent vessels are also possible. In contrast to medulla, cortical secretory activity is not associated with altered blood flow. However, neural elements are found in close proximity to cortical vessels, and the cortical vasculature responds to changes in O2 tension and to a number of pharmacological agents. In addition, several studies indicate that cortical secretory activity can be modulated by changes in blood flow. The response of both vasculatures to pharmacological agents is, in many instances, different from responses observed in other vascular beds. These data indicate that the adrenal has evolved unique vasoregulatory mechanisms, either because vasoactive compounds are present in such high concentration, or because blood flow plays an important role in the secretory process.

Hyperadrenergic states.

OBJECTIVE: To review the physiologic and pathophysiologic hyperadrenergic states and the pharmacologic use of sympathomimetic agents. DATA SOURCES: Pharmacologic and physiologic studies in experimental animals and humans. DATA EXTRACTION/SYNTHESIS: Plasma catecholamines are increased in a variety of clinical situations. Following major injury, catecholamines act to support vital organ perfusion and mobilize fuel substrates. However, with surgical trauma and during acute medical illnesses, such as myocardial infarction, catecholamine-induced physiologic changes can interact with underlying disease processes to result in clinically significant complications. Exogenous catecholamines are used to treat a variety of medical conditions, including anaphylaxis and various shock states. Available sympathomimetic agents differ in their availability to stimulate different subpopulations of adrenergic receptors. These differences permit the astute clinician to achieve specific physiologic end-points. Finally, plasma catecholamines are increased in patients with pheochromocytoma. This latter condition provides insights into the long-term effects of catecholamine excess. CONCLUSIONS: Based on knowledge of the pharmacology of sympathomimetic agents and the physiologic consequences of adrenergic receptor stimulation, it is possible to prevent undesirable catecholamine effects and to utilize these agents to achieve desired therapeutic goals.

Effect of acetylcholine infusion on adrenal vasculature and catecholamine secretion.

To evaluate effects of cholinergic receptor stimulation on regional adrenal blood flow (Q, radiolabeled microspheres) and catecholamine secretion, acetylcholine (ACh) was infused into pentobarbital-anesthetized, ventilated dogs. Unilateral adrenal denervation and placement of lumboadrenal catheters preceded intra-aortic infusion of 1) ACh alone (n = 6), 2) ACh plus hexamethonium (Hex) 20 mg/kg (n = 6), or 3) ACh plus atropine (Atr) (0.5 mg/kg) and Hex. ACh alone and in combination with Hex elicited similar dose-related (2, 20, and 100 mumol/min) increases in catecholamine secretion (181 +/- 61 to 1,055 +/- 229, 31,644 +/- 9,411, and 179,181 +/- 69,659 ng.min-1 x g medulla-1), whereas Hex and Atr together inhibited ACh-induced secretion by 95%. ACh caused marked medullary vasodilation (0.71 +/- 0.05 to 0.14 +/- 0.03 mmHg.ml-1 x min.100 g) in all three groups. To determine whether medullary vasodilation was due to incomplete muscarinic blockade, Hex-pretreated animals (n = 4) received ACh (100 mumol/min) and three increasing doses of Atr (0.5, 5, and 25 mg/kg). Catecholamine secretion was inhibited by all doses of Atr; however, vasodilation was blocked only by the two higher doses of Atr. These data suggest possible different mechanisms of muscarinic receptor-mediated catecholamine secretion and vasodilation.

Muscarinic cholinergic receptors in canine adrenal gland.

Muscarinic cholinergic receptor stimulation has been reported to modulate adrenal catecholamine and steroid secretion and influence medullary vascular tone. The present study was undertaken to localize and characterize muscarinic cholinergic receptor binding sites in canine adrenal medulla and cortex. Binding studies using semipurified membranes demonstrated specific, saturable binding of L-[benzilic-4,4'-3H(N)]-quinuclidinyl benzilate ([3H]QNB) in medulla, with a dissociation constant (KD) equal to 152 pM and estimated maximal binding sites (Bmax) equal to 179 fmol/mg protein. Displacement of [3H]QNB by cholinergic agents in order of decreasing potency was atropine, pirenzepine, oxotremorine, pilocarpine, and carbamylcholine, suggesting the receptor was M1 subtype, similar to sympathetic ganglion muscarinic receptors. Autoradiographic imaging studies demonstrated highly specific, homogeneous binding throughout the medulla. No specific binding was found in adrenal cortex. These results suggest that muscarinic effects on blood flow may be neurally mediated, rather than the result of stimulation of vascular muscarinic receptors. In medulla, muscarinic receptors are evenly distributed and modulate catecholamine secretion in all cells rather than subpopulations of cells as in other species. Absence of [3H]QNB binding in cortex argues against muscarinic receptor modulation of cortical steroid secretion.