Leukocyte activation during cardiopulmonary bypass: limitations of the inhibitory mechanisms and strategies

Cardiopulmonary bypass, initiates a generalised response, which is primarily defensive in nature. This response is self regulated and terminated spontaneously. Obvious problems are complement and leucocyte activation, but several other cascades are also stimulated, which interact, accentuate or modulate this response. These supporting cascades include, release of inflammatory cytokines, an activation of kallikrein system, clotting and fibrinolytic mechanisms, and arachidonic acid metabolism. Because of an effective autoregulatory mechanism, only a small proportion of patients (<3%), undergoing cardiopulmonary bypass are adversely effected by this process. Prognosis of these patients is often unpredictable, but in general, high risk patients are likely to suffer most. A number of specific and non specific artificial measures have been introduced to control postperfusion problems, resulting from this process. These control measures are usually effective against a specific component of this generalised problem, and often fail to achieve desired effects. Efficacy of control measures is further limited by a continued activation of complement and leucocytes, via interactions between the mentioned inflammatory cascades. In view of these limitations, we have introduced certain modifications in our previously reported control strategy. These include an early identification of high risk and susceptible individuals and using specific inhibitors of complement activation for both initial and terminal stages.     

Acute hyperglycemia attenuates nerve conduction velocity and nerve blood flow in male Sprague–Dawley rats: reversal by adenosine

Hyperglycemia is implicated to play a major role in development of diabetic neuropathy. Since most of the diabetics are hyperglycemic much before they develop full-blown diabetes, we felt, it would be very important to know the effects of acute hyperglycemia on nerve function so that early pathophysiological events could be understood and appropriate therapeutic intervention can be made. Moreover, effect of acute hyperglycemia on motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) is not known. Hence, we studied the effects of acute hyperglycemia on sciatic MNCV and sciatic NBF in healthy male Sprague-Dawley (SD) rats. Three different animal models of acute hyperglycemia (50% glucose (3 g kg(-1), i.v. (intra-venous) or i.p. (intra-peritoneally)) or 24 h post-streptozotocin (STZ) injected rats were used. Acute hyperglycemia but not mannitol or sucrose significantly attenuated MNCV and NBF. Adenosine (10 mg kg(-1), i.p.) prevented the acute hyperglycemia-induced attenuation of MNCV and NBF in all the three rat models of acute hyperglycemia. Adenosine effects were blocked by theophylline (50 mg kg(-1), i.p.) suggesting the role of adenosinergic receptor mediated mechanisms in acute hyperglycemia-induced neuropathy. Acute glucose administration in 8 weeks, STZ diabetic rats did not further affect MNCV or NBF. Adenosine (10 mg kg(-1), i.p.) did not produce any adverse effects on the blood pressure and heart rate. From the results, we conclude that acute hyperglycemia attenuates MNCV and NBF via an adenosinergic receptor-dependent mechanism.     

Comparison of exercise electrocardiography and quantitative thallium imaging for one-vessel coronary artery disease

The relative value of exercise electrocardiography and computer analyzed thallium-201 imaging was compared in 124 patients with 1-vessel coronary artery disease (CAD). Of these, 78 had left anterior descending (LAD), 32 right and 14 left circumflex (LC) CAD. In patients with no previous myocardial infarction (MI), thallium imaging was more sensitive than the electrocardiogram (78% vs 64%, p less than 0.01), but in patients with previous MI, sensitivity was similar. Further, thallium imaging was more sensitive only in LAD and LC disease. Redistribution was compared with ST-segment depression as a marker of ischemia. Only in patients with prior MI (76% vs 44%, p less than 0.01) and only in LC and right CAD did redistribution occur more often than ST depression. Thallium imaging was more accurate in localizing stenoses than the electrocardiogram (p less than 0.001), but did not always correctly predict coronary anatomy. Septal thallium defects were associated with LAD disease in 84%, inferior defects with right CAD in 40% and posterolateral lesion defects with LC CAD in 22%. The results indicate the overall superiority of thallium imaging in 1-vessel CAD compared with exercise electrocardiography; however, there is a wide spectrum of extent and location of perfusion defects associated with each coronary artery. Thallium imaging complements coronary angiography by demonstrating the functional impact of CAD on myocardial perfusion.     

Gastric acid and pepsin secretion in response to modified sham feeding in active and inactive duodenal ulcer disease

Gastric secretion of acid and pepsin were studied under basal conditions, in response to modified sham feeding (MSF), and in response to pentagastrin in 15 male controls and in 11 and 10 male patients with active and inactive duodenal ulcer disease, respectively. In general, patients with ulcer disease produced more acid and pepsin than controls. No differences between the two ulcer groups were found for basal and pentagastrin-stimulated secretions. The response patterns to MSF, however, were different in the two groups. After an early peak, acid and pepsin responses rapidly decreased, approaching basal level in patients with active duodenal ulcer and in controls. In patients with inactive disease, however, the decrease was less marked, and in some patients the secretion continued to increase for 60 min. When expressed as fractions of the responses to pentagastrin, the acid and pepsin responses during the fourth 15-min period were significantly greater in patients with inactive duodenal ulcer disease than in patients with active disease and in controls. The findings indicate that the gastric response to vagal stimulation is different in patients with active and inactive duodenal ulcer disease.     

Extremely High Body Mass Index is not a Contraindication to Laparoscopic Gastric Bypass

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is an effective operation for morbidly obese patients who have failed conservative weight loss treatments. It is currently indicated for patients with BMI >40 kg/m² or >35 with significant co-morbidities. Controversy exists whether there is an upper limit to BMI beyond which this operation should not be performed. Methods: Between April 1999 and February 2001, 82 patients (19 male, 63 female) underwent LRYGBP. Average age was 43.6, and average BMI was 56 kg/m². These patients were divided into those with BMI <60 and those with BMI ≥60 kg/m². Results:There were 61 patients with BMI <60 and 21 patients with BMI ≥60. The groups were similar in age, gender, distribution or incidence of co-morbid conditions (diabetes, coronary artery disease, hypertension, sleep apnea, asthma) between the groups. The BMI ≥60 group had a significantly longer length of stay (6.6 days vs 5.3 days, P <0.05), and only 1 patient (BMI 85) developed an anastomotic leak and died. 2 patients in this group (BMI 62 and 73) developed small bowel obstruction requiring lysis of adhesions. 1 patient in the BMI <60 group developed a gastrojejunal stricture requiring balloon dilatation. Conclusion: While patients with a BMI ≥60 are at higher risk for postoperative complications, they are also at higher risk from continued extreme obesity. In our series, 85% of these patients had an uneventful postoperative course and began shedding excess weight. BMI ≥60 should not be a contraindication for LRYGBP.     

Retroperitoneal robotic renal surgery: technique and early results

We describe a robotic retroperitoneal approach to renal surgery, optimized in porcine and cadaveric models, and applied to human patients. A retroperitoneal approach for robotic kidney surgery was developed in nonsurvival porcine and a fresh cadaver models, and then utilized in ten patients (three partial nephrectomy, three radical nephrectomy, two simple nephrectomy, one pyeloplasty, one cryoablation). Retroperitoneal access was successfully achieved for robotic renal procedures in six pigs and a human cadaver. Ten human patients (mean age 56 years, range 36–72 years) then underwent a successful retroperitoneal approach for robotic renal surgery. Mean console time was 166 (120–300) min. Mean blood loss was 82 (50–100) ml and average hospital stay was 2.6 (1–5) days. Pathology demonstrated clear cell renal cell carcinoma (four), papillary renal cell carcinoma (two), and xanthogranulomatous pyelonephritis (two). One patient with xanthogranulomatous pyelonephritis required open conversion for failure to progress due to dense adhesions. A retroperitoneal approach is a safe and feasible alternative to a transperitoneal approach for robotic renal surgery, including radical nephrectomy, partial nephrectomy, pyeloplasty, and cryoablation. M. N. Patel and S. A. Kaul contributed equally to this work.     

Nitrous oxide anxiolysis for elective cesarean section

STUDY OBJECTIVE: To determine if inhaled 40% nitrous oxide (N(2)O) via facemask is an effective anxiolytic in women undergoing elective cesarean section under spinal anesthesia. STUDY DESIGN: Prospective, randomized, double-blinded study. SETTING: Tertiary-care women's hospital. PATIENTS: Sixty American Society of Anesthesiologists physical status I and II patients scheduled for elective cesarean section under spinal anesthesia. INTERVENTIONS: Patients were randomized to 2 groups to receive either 100% O2 via facemask or 40% N2O in O2 via facemask. MEASUREMENTS: Vital signs (blood pressure, heart rate, and oxygen saturation) and measured variables (visual analog scale [VAS] anxiety, VAS pain, and sedation scores) were obtained at specific periods during the procedure (preoperatively, entering the operating room, spinal injection, skin incision, uterine incision, delivery, and at the conclusion of the surgical procedure). In addition, surgical time and delivery time, mean dose and percentage of patients requiring ephedrine or phenylephrine boluses, the emesis rate, and Apgar scores were measured. MAIN RESULTS: No differences were noted with respect to maternal mean blood pressure, heart rate, pulse-oximeter oxygen saturation, and sedation or VAS pain scores during the measured periods. No differences were noted in surgical and delivery times, mean dose, or percentage of patients who required ephedrine or phenylephrine to maintain maternal blood pressure, the emesis rate, or 1- and 5-minute Apgar scores. Mean anxiety scores for the N2O group were significantly lower at the time of spinal injection, skin incision, and uterine incision. Multivariate analysis of variance for high-anxiety patients (> or =50 VAS) revealed significantly lower VAS scores in the N2O group, compared with the O2 group again at spinal injection, skin incision, and uterine incision. CONCLUSIONS: Inhaled 40% N2O via facemask provides effective anxiolysis in women undergoing elective cesarean section under spinal anesthesia in patients with high anxiety (> or =50 VAS) at the time of spinal injection, skin incision, and uterine incision.     

Six-Month Prophylaxis Is Cost Effective in Transplant Patients at High Risk for Cytomegalovirus Infection

The risk of late-onset cytomegalovirus (CMV) infection remains a concern in seronegative kidney and/or pancreas transplant recipients of seropositive organs despite the use of antiviral prophylaxis. The optimal duration of prophylaxis is unknown. We studied the cost effectiveness of 6- versus 3-mo prophylaxis with valganciclovir. A total of 222 seronegative recipients of seropositive kidney and/or pancreas transplants received valganciclovir prophylaxis for either 3 or 6 mo during two consecutive time periods. We assessed the incidence of CMV infection and disease 12 mo after completion of prophylaxis and performed cost-effectiveness analyses. The overall incidence of CMV infection and disease was 26.7% and 24.4% in the 3-mo group and 20.9% and 12.1% in the 6-mo group, respectively. Six-month prophylaxis was associated with a statistically significant reduction in risk for CMV disease (HR, 0.35; 95% CI, 0.17 to 0.72), but not infection (HR, 0.65; 95% CI, 0.37 to 1.14). Cost-effectiveness analyses showed that 6-mo prophylaxis combined with a one-time viremia determination at the end of the prophylaxis period incurred an incremental cost of $34,362 and $16,215 per case of infection and disease avoided, respectively, and $8,304 per one quality adjusted life-year gained. Sensitivity analyses supported the cost effectiveness of 6-mo prophylaxis over a wide range of valganciclovir and hospital costs, as well as variation in the incidence of CMV disease. In summary, 6-mo prophylaxis with valganciclovir combined with a one-time determination of viremia is cost effective in reducing CMV infection and disease in seronegative recipients of seropositive kidney and/or pancreas transplants.Cytomegalovirus (CMV) infection remains one of most common opportunistic infections in solid organ transplant patients despite availability of specific and efficacious anti-viral drugs.^1,2 Solid organ transplant patients who have a negative CMV serology and receive an organ from a positive CMV serologic donor (D+/R−) have the highest incidence of CMV disease with and without prophylaxis.^2–5 Although the risk for CMV disease persists for life, the majority of cases occur shortly after completion of prophylaxis, often within the first year after transplant.⁶ CMV disease causes significant morbidity, increases mortality, and is associated with inferior transplant outcomes, particularly in the case of kidney transplantation.^7–10 Furthermore, the presence of CMV disease is one of the most frequent infectious causes of hospitalization early after transplantation, increasing the total cost of kidney transplantation and reducing its overall effectiveness.^7,11–13Valganciclovir (VGCV) is an effective anti-CMV agent for prophylaxis and treatment of CMV disease that is widely used in transplantation.^2,14–16 Although the recommended dose for CMV prophylaxis is 900 mg daily adjusted for renal function, a recent study showed that VGCV at 450 mg daily provides similar drug exposure compared with oral ganciclovir (GCV) at 1000 mg three times daily in kidney transplant patients, a dose similarly effective for CMV prophylaxis.^2,17 In most studies, VGCV prophylaxis consisted of 100 d after transplant, after which time the risk of CMV infection and disease increased.^2,18,19 Extending the duration of VGCV prophylaxis beyond the early post-transplant period may abrogate this transient increase in the risk of infection and disease.^20,21 In this regard, the optimal duration of prophylaxis for CMV D+/R− patients has not been determined and is the subject of ongoing study.²² Cost, efficacy, and safety are important factors in determining the optimal duration of VGCV prophylaxis. Over the past two decades, various strategies have been used including pre-emptive versus universal prophylaxis and shorter versus longer period of prophylaxis.^20,21,23,24 Although several clinical studies comparing universal prophylaxis versus pre-emptive anti-viral therapy have found similar efficacy and cost in managing CMV infection across various combinations of donor and recipient CMV serologic status, two meta-analyses did find that the use of universal prophylaxis was associated with reduced risk for CMV disease and death.^23–26This study is based on a single center experience comparing two CMV prophylaxis strategies. We report here the clinical outcome and cost-effectiveness analyses of 6- versus 3-mo VGCV prophylaxis in CMV D+/R− de novo kidney and/or pancreas transplant patients.     

Pancreas after living donor kidney transplants in diabetic patients: impact on long-term kidney graft function

Abstract:  In this single-institution study, we compared outcomes in diabetic recipients of living donor (LD) kidney transplants that did vs. did not undergo a subsequent pancreas transplant. Of 307 diabetic recipients who underwent LD kidney transplants from January 1, 1995, through December 31, 2003, a total of 175 underwent a subsequent pancreas after kidney (PAK) transplant; 75 were deemed eligible (E) for, but did not receive (for personal or financial reasons), a PAK, and thus had a kidney transplant alone (KTA); and 57 deemed ineligible (I) for a PAK because of comorbidity also had just a KTA. We analyzed the three groups (PAK, KTA-E, KTA-I) for differences in patient characteristics, glycemic control, renal function, patient and kidney graft survival rates, and causes of death. Kidney graft survival rates (actuarial) were similar in the PAK vs. KTA-E groups at one, five, and 10 yr post-transplant: 98%, 82%, and 67% (PAK) vs. 100%, 84%, and 62% (KTA-E) (p = 0.9). The long-term (greater than four yr post-transplant) estimated glomerular filtration rate (GFR) was higher in the PAK than in the KTA-E group: 53 ± 20 mL/min (PAK) vs. 43 ± 16 mL/min (KTA-E) (p = 0.016). The patient survival rates were also similar for the PAK and KTA-E groups. We conclude that the subsequent transplant of a pancreas after an LD kidney transplant does not adversely affect patient or kidney graft survival rates; in fact, it is associated with better long-term kidney graft function.