Resúmenes semana junio 27 a Julio 3,2002
June 2002 • Volume 3 • Number 3
Original Reports
Predictors of pain during invasive medical procedures
David Sheffield† [MEDLINE LOOKUP]
Susan Lutgendorf‡ [MEDLINE LOOKUP]
Elvira Lang§ [MEDLINE LOOKUP]
Abstract
This study explored whether cardiovascular response and heart rate response to surgical stress were related to pain during percutaneous transcatheter diagnostic and therapeutic peripheral vascular and renal interventions. One hundred twenty-nine patients, 61 men and 68 women, provided repeated measures of pain on a 0 to 10 scale every 15 minutes during and at the end of the procedure. We tested 2 hypotheses: (1) baseline blood pressure and heart rate predict pain report and (2) initial procedural changes in blood pressure and heart rate predict pain report. Results of regression analysis showed that heart rate response is a significant independent predictor of pain regardless of whether pain is defined as the maximum level during the procedure or as the pain level at the end. Baseline pain, anxiety, and heart rate were significantly correlated to maximum pain report but did not enter the final model as significant independent predictors. We also found that patients whose heart rate increased during surgery from their baseline level had significantly lower pain report than those who did not show an increase. Neither baseline blood pressure nor blood pressure changes were significant predictors of pain level. Thus, we concluded that heart rate response is a powerful negative predictor of procedural pain even after controlling for baseline variables, type of procedure, and units of pain medication. © 2002 by the American Pain Society
Publishing and Reprint Information / TOP- Received June 5, 2001.
- Revised September 6, 2001.
- Accepted September 6, 2001.
- From the *Division of Public Health Services and Research, University of Florida College of Dentistry, and †Department of Medicine, University of Florida, Gainesville, FL; ‡Department of Psychology, University of Iowa, Iowa City, IA; and §Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA.
- Supported by NIMH RO1-MH56274 and NCCAM RO1-AT 00002-04. Dr Sheffield was supported by NHLBI R01 HL64580.
- Address reprint requests to Henrietta Logan, PhD, 1600 SW Archer Road, Box 100404, Gainesville, FL 32610. E-mail:
- © 2002 by the American Pain Society
June 2002 • Volume 16 • Number 3
Original Articles
Renal tubular injury after infrarenal aortic aneurysm repair
D.R. Digby Roberts, FRCA [MEDLINE LOOKUP]
Christopher P. Snowden, FRCA [MEDLINE LOOKUP]
Abstract / TOP
Objective: To investigate markers of tubular injury (glutathione-S-transferase [GST] isoforms) as early markers for renal damage in patients undergoing abdominal aortic aneurysm repair.
Design: Prospective study.
Setting: Regional teaching hospital.
Participants: Eight consecutive patients undergoing elective infrarenal abdominal aortic aneurysm repair.
Interventions: All patients received a standard anesthetic technique including a dopamine infusion (3 µg/kg/min) but without supplemental renoprotective agents. Urine and blood samples were taken at induction, at 1 hour and 3 hours after limb reperfusion, and on days 1 and 2 postoperatively. Urine microalbumin and creatinine concentrations were measured using standard assays, and urine -GST and -GST enzyme measurements were performed by a commercial immunoassay (Biotrin, Biotrin International Ltd., Co., Dublin, Ireland).
Measurements and Main Results: Five patients (63%) showed a postoperative elevation of serum creatinine (median increase from baseline, 35.4%; range, 8.3% to 50.6%) that was associated with significant elevations of urinary microalbumin-to-creatinine, -GST-to-creatinine, and -GST-to-creatinine ratios soon after clamp removal. The remaining 3 patients showed no increase in serum creatinine or urine proteins. Peak -GST-to-creatinine levels were different between the 2 groups. The peak levels of GST enzymes were significantly (r2 > 80%) associated with the percent increase in serum creatinine from baseline.
Conclusion: Urinary GST-to-creatinine ratios are a sensitive early biomarker for renal injury after infrarenal abdominal aortic aneurysm repair.
Copyright 2002, Elsevier Sceince (USA). All rights reserved.
- From the Department of Anaesthetics, Northampton Hospital; Department of Anaesthetics, Freeman Hospital; and Dept. of Surgical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.
- Address reprint requests to Christopher P. Snowden, FRCA, Department of Anaesthetics, Freeman Hospital, Newcastle upon Tyne, NE7 7DN UK. E-mail: .
- Copyright 2002, Elsevier Sceince (USA). All rights reserved.
June 2002 • Volume 16 • Number 3
Original Articles
Neuroprotection is associated with -adrenergic receptor antagonists during cardiac surgery: Evidence from 2,575 patients
Alina Grigore, MD [MEDLINE LOOKUP]
John K. Amory, MD [MEDLINE LOOKUP]
Mark A. Gerhardt, MD, PhD [MEDLINE LOOKUP]
William D. White, MPH [MEDLINE LOOKUP]
Peter K. Smith, MD [MEDLINE LOOKUP]
Debra A. Schwinn, MD [MEDLINE LOOKUP]
J. G. Reves, MD [MEDLINE LOOKUP]
Mark F. Newman, MD [MEDLINE LOOKUP]
the Duke University Perioperative Organ Protection Consortium*
Abstract / TOP
Objective: To determine the impact of perioperative -adrenergic receptor (AR) antagonist administration on neurologic complications.
Design: Observational database analysis.
Setting: A clinical investigation at a single tertiary academic medical center.
Participants: Elective coronary artery bypass graft surgical patients operated on in the period 1994-1996.
Interventions: Patients were divided into 2 groups: (1) patients given AR antagonist–blocking drugs in the perioperative period, including during operation, and (2) patients not given AR antagonists.
Measurements and Main Results: AR antagonist use in 2,575 consecutive patients undergoing coronary artery bypass graft surgery (1994-1996) was determined using the Cardiovascular Database and Anesthesia Information System Database. Outcome variables were postoperative stroke, coma, and transient ischemic attack. Of patients, 113 (4.4%) had postoperative neurologic complications, including stroke (n = 44), coma (n = 12), and transient ischemic attack (n = 3). Of patients, 2,296 (89%) received perioperative AR antagonist therapy, and 279 (11%) did not. Adverse neurologic events occurred in 3.9% (n = 90) of patients who received perioperative AR antagonists and 8.2% (n = 23) of patients who did not receive AR antagonists (odds ratio, 0.45; 95% confidence interval, 0.28 to 0.73; p = 0.003, unadjusted.) Severe neurologic outcomes (stroke and coma) occurred in 1.9% (n = 44) of patients who received AR antagonists and 4.3% (n = 12) of patients who did not receive AR antagonists (odds ratio, 0.43; 95% confidence interval, 0.23 to 0.83; p = 0.016).
Conclusion: Use of -adrenergic antagonists was associated with a substantial reduction in the incidence of postoperative neurologic complications. A prospective randomized trial is needed to verify this potentially important neuroprotective strategy in cardiac surgery.
Copyright 2002, Elsevier Science (USA). All rights reserved.
- *See Acknowledgment.
- From the Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, Duke University Heart Center, Durham, NC; Department of Medicine, University of Washington, Seattle, WA; Department of Anesthesiology, Ohio State University Medical Center, Columbus, OH; Department of Surgery, Duke University Medical Center, Durham, NC; and Department of Anesthesiology, Medical University of South Carolina, Charleston, SC.
- Supported by NIH grants RO1-AG09663 (J.G.R.), 1RO1-HL54316 (M.F.N.), RO1-HL57447 (D.A.S.), KO2-AG00545 (D.A.S.), #HL57447 (D.A.S.), and AG00745 (D.A.S.), American Heart Association Grant-In-Aid, #95010970 (M.F.N.), and NIH MOI-RR-30.
- Presented in part at the Society of Cardiovascular Anesthesiologists 21st Annual Meeting, Chicago, IL, April 24-28, 1999.
- Address reprint requests to Mark F. Newman, MD, Duke University Medical Center, Box 3094, Durham, NC 27710. E-mail:
- Copyright 2002, Elsevier Science (USA). All rights reserved.
June 2002 • Volume 16 • Number 3
Editorial
Pheochromocytoma: Specialist cases that all must be prepared to treat?
Sections
- References
- Publishing and Reprint Information
THIS ISSUE IS rich with content pertinent to the management of pheochromocytoma, with special attention to cases arising from the heart. There are 2 interesting case reports, a focused review article, and expert commentary on the case conference. The case reports raise the question of whether experienced specialists are needed to manage a patient with a pheochromocytoma or whether the average well-trained anesthesiologist is capable of managing such cases.
Medical progress on many fronts has helped change the management of pheochromocytoma from that of a risky undertaking to one approaching routine. Regardless of these advances, an unsuspected case can be encountered, possibly resulting in disaster. This situation is analogous to that with malignant hyperthermia, a disease process in which the underlying abnormalities now are well understood down to the molecular level. Although malignant hyperthermia once carried significant mortality, the management of susceptible individuals and the treatment of intraoperatively diagnosed cases are well worked out and within the scope of expertise of all anesthesiologists. The same is becoming true for pheochromocytoma, as modern practitioners are able to remove these tumors with near-zero mortality compared with a fatality rate of about 50% just 2 or 3 decades ago.
The diagnosis of pheochromocytoma historically has been problematic because of imperfect sensitivity and especially specificity of laboratory tests. A high index of suspicion is necessary to determine when to screen for this rare disease, responsible for only 0.1% of all cases of hypertension. Absence of headache, sweating, or palpitations is suggested to virtually eliminate the diagnosis, but these symptoms are common in clinical practice.1 Investigations into the varied metabolic pathways of catecholamines have permitted the discrimination, at least in part, of the metabolism of intraneuronally derived catechols from those that are released from a pheochromocytoma or normal adrenal gland directly into the systemic circulation. Screening for plasma metanephrines and normetanephrines, derived preferentially from circulating catecholamines, has become the best test to rule out pheochromocytoma. Although still not universally available at all centers, screening blood tests for these catecholamine metabolites are suggested to have sensitivity and negative predictive values approaching 100%, exceeding that of urine screening tests and serum tests for other metabolites or catecholamines themselves.2 Consequently, diagnostic protocols should be simplified and improved. The sensitivity of these tests is now being combined with genetic screening of potentially susceptible individuals.3 Families prone to pheochromocytoma, such as those with multiple endocrine neoplasia type II, von Hippel–Lindau disease, and neurofibromatosis type 1, may have their tumors identified earlier, permitting safer surgical treatment before the tumors cause greater cardiovascular derangement.
Surgical advances in the treatment of pheochromocytoma have accompanied improvements in the localization of tumors. Resection of pheochromocytoma previously required a large intra-abdominal incision, necessitated by the need to search for contralateral and extra-adrenal coexisting tumors. Tumors were identified by palpation of the opposite adrenal gland and periaortic regions while the anesthesiologist observed accompanying hemodynamic changes. Extra-adrenal neoplasms, constituting 10% to 20% of some large series of pheochromocytomas, were difficult to diagnose, presented later in the course of illness, and were more metabolically active, making their resection much more problematic. Significant progress has been made in various imaging studies. Computed tomography is still the best modality to image adrenal tumors, whereas magnetic resonance imaging may have some advantages for extra-adrenal tumors.3 These enhancements in imaging have led to an increased diagnosis of adrenal incidentalomas, requiring the use of the better screening techniques for catecholamine metabolites previously discussed. The addition of radionuclide scanning offers superior specificity in imaging pheochromocytomas, and is readily accomplished using radioactive iodine-labeled meta-iodobenzylguanidine (MIBG), which is taken up by these active tumors. Ongoing research is underway with other labels and positron emission tomography. These improvements in imaging and localization have allowed surgeons to eliminate the use of large incisions and the need to search the abdomen for additional tumors. Smaller and less morbid posterior or flank incisions are often employed for tumor resection. Advances in minimally invasive surgical technique now permit the removal of pheochromocytomas laparoscopically without any increase in the incidence of adverse intraoperative hemodynamic sequelae.4
Accompanying these advances in diagnosis and surgery for this disease have been many advances in anesthesiology, including better monitors and monitoring techniques, better drugs, and a parallel improvement in the quality and training of anesthesiologists. The quality and expertise of modern anesthesiology practice may be evident by the noteworthy omission of the specialty at an interdisciplinary National Institutes of Health conference on research and advances in care of patients with pheochromocytoma.3
The first major advance in the treatment of pheochromocytoma resulted from the preoperative preparation of the patient using the -blocking drug phenoxybenzamine. Restoration of circulating blood volume, prevention of dangerous hypertensive episodes before and during surgery, and correction of potentially dangerous myocardial toxicity from the excess circulating catecholamines have been the major contributions of this preoperative therapy. Phenoxybenzamine remains the gold standard against which other therapies must be compared. There is still dogmatic insistence on its use for at least 2 weeks preoperatively, although many experts have retreated from this stance and find a shorter treatment period adequate.5,6
Many other preoperative blockade approaches have been used, including more selective 1-blocking drugs (eg, prazosin or terazosin), calcium channel–blocking drugs, and labetalol with its combined - and –blocking properties. A large series reported by an advocate of selective 1-blockade (prazosin) failed to show any difference in outcome between patients treated with -blockade and patients who received no -blockade at all.6 It is possible that better understanding of this disease and improved ability to detect and treat intraoperative changes have made the preoperative preparatory phase a less crucial issue for most cases of pheochromocytoma.
Metyrosine ( methyl para-tyrosine) blocks tyrosine hydroxylase, the rate-limiting step in the synthesis of catecholamines. As such, metyrosine has direct application to the treatment of pheochromocytoma as an adjunct to the use of -blockade.7,8 This drug has been available for clinical use for several decades and although used routinely at some centers, it is ignored too often in others.9 Side effects are unpleasant for the patient, so noncompliant patients may present for surgery. The elegance of this approach is that catecholamine levels are lowered throughout the body, leading to better control of preoperative and intraoperative hemodynamic disturbances.7,8
It is this author's opinion that the length of preoperative treatment needs to be tailored to the patient's condition. The existence of cardiac dysfunction, although rare, is an indication for prolonged treatment with -blockade. A few days of treatment are probably is sufficient for most other patients because this is likely to allow some reregulation of -adrenergic receptors to more normal levels. Unpredictable responses to -adrenergic agonists are more likely without a brief period of preoperative blockade, making the treatment of intraoperative hypotension problematic. The author has found metyrosine to be a highly useful adjuvant therapy. It is the most elegant therapy and comes the closest to a medical cure for the patient (metyrosine is the treatment for metastatic and inoperable pheochromocytoma). The intraoperative course of patients has been hemodynamically smoother in the author's last 25 to 35 cases, when metyrosine was used preoperatively in combination with -blockade.
There are 2 major sources of catecholamine release that cause concern during the management of the patient with pheochromocytoma. Chronic high levels of circulating catecholamines originating from the tumor eventually lead to an excess of catecholamines in the termini of all sympathetic neurons. This overload is the result of catecholamine reuptake mechanisms that are present in sympathetic nervous system neurons, normally used to terminate the effects of synaptically released norepinephrine. This explanation has been validated by work examining dihydroxyphenylglycol (DHPG), a deaminated metabolite of norepinephrine formed mainly in sympathetic neurons and not in adrenal tissue. DHPG levels have been correlated with hypertensive crises, suggesting that catecholamine release from the peripheral neurons is the cause of these episodes and not necessarily release from the tumor itself.10 As a consequence of such enhanced neuronal stores of norepinephrine, any condition that leads to a stimulation of the sympathetic nervous system (eg, anxiety or pain) results in excessive release of transmitter and an exaggerated physiologic response, which can be just as problematic as the unpredictable release of vasoactive hormones from the tumor itself. The conditions that reliably stimulate a sympathetic response in the operating room are, however, relatively predictable (arterial catheter insertion, intubation, incision) and can be approached with caution, preparation, and vigilance.
The direct release of hormones from the pheochromocytoma has been reported to occur intraoperatively with positioning changes, insufflation of the peritoneal cavity during laparoscopy, and tumor manipulation itself. There may be other unknown factors that could stimulate tumoral catecholamine release. Circulating concentrations of epinephrine and norepinephrine can be 1 to 2 orders of magnitude higher than the normal levels.5,11 Regardless of the degree and duration of preoperative preparation, actions may need to be taken in the operating room to deal with significant catecholamine-induced physiologic insults occurring during the course of the procedure. The ability of anesthesiologists to meet this challenge is facilitated by using drugs with which they have considerable experience. Most practitioners use nitroprusside for initial blood pressure control because its rapid onset and short half-life make it a practical therapeutic option. Many other drugs have been reported to be effective, including trimethaphan camsylate, nitroglycerin, nicardipine, and fenoldopam. The short-acting -blocker phentolamine, magnesium, and esmolol can be useful adjuncts for particularly difficult cases. Additionally, rapid titration of inhalation anesthetic concentration can be brought to bear, especially facilitated by the newer less soluble agents, sevoflurane and desflurane. The author has found the combination of intravenous and inhalation drugs to be safer because they are more rapidly titratable and less likely to result in overshoot hypotension.
Regional anesthesia can also be used effectively, but its use must be balanced against the risk of adverse hemodynamic sequelae. Preoperative insertion runs the risk of hypertension during placement, although the author has not observed this effect with adequate sedation and an experienced practitioner. Use of local anesthetic may help to block sympathetic nervous system responses to stimulation but may complicate fluid management after adrenal vein ligation, leading to aggravation of hypotension.
Several other issues can make the perioperative course of pheochromocytoma more complicated. Rare tumors produce only epinephrine, resulting in vastly different symptoms, such as hypotensive episodes. Release of other substances, such as dopamine, also leads to unpredictable responses. Some may argue that these patients should be sent to centers with extensive case experience. A strong argument can also be made, however, that most skilled and attentive anesthesiologists, using the array of anesthetic agents, adjuvants, and cardiovascular drugs now available, should be able to manage a patient with pheochromocytoma who has been appropriately prepared for surgery.
As shown by the case reports in this issue, the possibility of encountering an undiagnosed, and untreated, pheochromocytoma always exists. Vigilant anesthesiologists need to be prepared and knowledgeable in the treatment of these patients, just as they need to be for a new case of malignant hyperthermia.