Aonghus O'Donnell

Fenoldopam: renal and splanchnic effects in patients undergoing coronary artery bypass grafting

Impairment of renal and splanchnic perfusion during and after cardiopulmonary bypass may be responsible for acute renal failure and endotoxin‐mediated systemic inflammation, respectively. We hypothesised that fenoldopam, a selective dopamine receptor agonist, would preserve renal function after cardiopulmonary bypass through its selective renal vasodilatory and natriuretic effects, and increase gastrointestinal mucosal perfusion by selective splanchnic vasodilation. We examined the effects of fenoldopam on haemodynamic parameters, creatinine clearance, fractional excretion of sodium, urine output, free water clearance and gastric mucosal pH in 31 patients undergoing elective coronary revascularisation. Patients were randomly assigned to receive continuous infusions of fenoldopam 0.1 µg.kg−1.min−1 (n = 16) or placebo (n = 15). Renal parameters were measured: during a 24‐h period before hospital admission, during cardiopulmonary bypass, from completion of cardiopulmonary bypass until 4 h later, from 4 to 8 h after cardiopulmonary bypass, and from 8 to 14 h after cardiopulmonary bypass. Gastric intramucosal pH was measured using a gastric tonometer before, during and after cardiopulmonary bypass. In the placebo group, but not the fenoldopam group, mean (SD) creatinine clearance decreased after separation from cardiopulmonary bypass, from 107 (36) to 71 (22) ml.min−1 (p < 0.01) and from 107 (36) to 79 (26) ml.min−1 (p < 0.01) for the 0–4 h and 4–8 h intervals after cardiopulmonary bypass, respectively. Changes in intramucosal pH were similar in both groups. The findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect in patients undergoing cardiopulmonary bypass.

Aprotinin decreases the incidence of cognitive deficit following CABG and cardiopulmonary bypass: A pilot randomized controlled study

PurposeCognitive deficit after coronary artery bypass surgery (CABG) has a high prevalence and is persistent. Meta-analysis of clinical trials demonstrates a decreased incidence of stroke after CABG when aprotinin is administrated perioperatively. We hypothesized that aprotinin administration would decrease the incidence of cognitive deficit after CABG.MethodsThirty-six ASA III–IV patients undergoing elective CABG were included in a prospective, randomized, single-blinded pilot study. Eighteen patients received aprotinin 2 × 106 KIU (loading dose), 2 × 106 KIU (added to circuit prime) and a continuous infusion of 5 × 105 KIU·hr−1. A battery of cognitive tests was administered to patients and spouses (n = 18) the day before surgery, four days and six weeks postoperatively.ResultsFour days postoperatively new cognitive deficit (defined by a change in one or more cognitive domains using the Reliable Change Index method) was present in ten (58%) patients in the aprotinin group compared to 17 (94%) in the placebo group [95% confidence interval (CI) 0.10–0.62,P = 0.005); (P = 0.01)]. Six weeks postoperatively, four (23%) patients in the aprotinin group had cognitive deficit compared to ten (55%) in the placebo group (95% CI 0.80−0.16,P = 0.005); (P = 0.05).ConclusionIn this prospective pilot study, the incidence of cognitive deficit after CABG and cardiopulmonary bypass is decreased by the administration of high-dose aprotinin.RésuméObjectifLe déficit cognitif qui survient après un pontage aortocoronarien (PAC) persiste seion une forte prévalence. Une méta-analyse d’essais cliniques démontre une incidence réduite d’accident vasculaire cérébral après un PAC quand l’aprotinine périopératoire est administrée. Nous avons émis l’hypothèse que l’aprotinine réduirait l’incidence de déficit cognitif après un PAC.MéthodeTrente-six patients, d’état physique III–IV selon l’ASA, devant subir un PAC réglé, ont été inclus à l’étude pilote, prospective, randomisée et à simple insu. Dix-huit patients ont reçu 2 × 106 UIK d’aprotinine (dose de charge), 2 × 106 UIK (ajouté au circuit d’amorce) et une perfusion continue de 5 × 105 UIK·h−1. Une batterie de tests cognitifs a été administrée aux patients et à leurs conjoints (n = 18) le jour précédant l’opération, quatre jours et six semaines après l’opération.RésultatsQuatre jours après l’opération, un nouveau déficit cognitif (défini par une modification dans au moins un domaine de connaissances selon la méthode de l’index fiable de changement) était présent chez dix (58 %) patients ayant eu de l’aprotinine, comparativement à 17 (94 %) du groupe placebo [intervalle de confiance de 95 % (IC) 0, 10–0,62, P = 0,005) ; (P = 0,01)]. Six semaines après l’opération, quatre (23 %) patients du groupe aprotinine présentaient un déficit cognitif comparativement à dix (55 %) du groupe placebo (IC de 95 % 0,80−0, 16,P = 0,005) ; (P= 0,05).ConclusionL’étude pilote prospective montre que l’incidence de déficit cognitif après un PAC et une circulation extracorporelle est réduite par l’administration d’aprotinine à doses élevées.

Plasma concentrations of nitric oxide products and cognitive dysfunction following coronary artery bypass surgery

Background and objective: Prospective longitudinal studies now indicate that cognitive dysfunction following coronary artery bypass surgery (CABG) is both common and persistent. This dysfunction is due in part to the inflammatory response and cerebral ischaemia‐reperfusion, with nitric oxide (NO) as an important mediator of both. We hypothesized that a clinically significant association exists between plasma concentrations of nitrate/nitrite (Symbol/Symbol) and cognitive dysfunction after CABG. Symbol. No caption available. Symbol. No caption available. Methods: Cognitive assessment was performed on 36 adult patients the day before CABG, on the fourth postoperative day and 3 months postoperatively. Patient spouses (n = 10) were also studied. Results: A new cognitive deficit was present in 22/36 (62%) 4 days postoperatively and in 16/35 (49%) of patients, 3 months postoperatively. Patients who had cognitive dysfunction 3 months postoperatively were more likely to have cognitive dysfunction and increased plasma Symbol/Symbol concentrations compared to the non‐deficit group preoperatively (22.6 (9.2) vs. 27.6 (8.4)) (P = 0.002). Plasma NOx (Symbol plus Symbol) concentrations were greater in patients with cognitive dysfunction 3 months postoperatively, 2 h (24.2 (6.3) vs. 19.1 (5.2)) (P = 0.002), and 12 h postoperatively (24.8 (7.6) vs. 18.8 (5.6)) (P = 0.001). There was, however, a time course similarity in NOx elevations for both deficit and non‐deficit groups. Conclusions: Perioperative plasma NOx concentrations do not serve as an effective biomarker of cognitive deficit after CABG.

Dopexamine increases internal mammary artery blood flow following coronary artery bypass grafting

OBJECTIVE Vasoactive agents and inotropes influence conduit-coronary blood flow following coronary artery bypass grafting (CABG). It was hypothesized that dopexamine hydrochloride, a dopamine A-1 (DA-1) and beta(2) agonist would increase conduit-coronary blood flow. A prospective randomized double blind clinical trial was carried out to test this hypothesis. DA-1 receptors have previously been localized to human left ventricle. METHODS Twenty-six American Society of Anaesthesiology class 2-3 elective coronary artery bypass graft patients who did not require inotropic support on separation from cardiopulmonary bypass (CPB) were studied. According to a randomized allocation patients received either dopexamine (1 microg/kg per min) or placebo (saline) by intravenous infusion for 15 min. Immediately prior to and at 5,10 and 15 min of infusion, blood flow through the internal mammary and vein grafts (Transit time flow probes, Transonic Ltd.), heart rate, cardiac index, mean arterial pressure and pulmonary haemodynamics were noted. The data were analysed using multivariate analysis of variance. RESULTS Low-dose dopexamine (1 microg/kg per min) caused a significant increase in mammary graft blood flow compared to placebo at 15 min of infusion (P=0.028, dopexamine group left internal mammary artery (LIMA) flow of 43.3+/-14.2 ml/min, placebo group LIMA flow at 26.1+/-16.3 ml/min). Dopexamine recipients demonstrated a non-significant trend to increased saphenous vein graft flow (P=0.059). Increased heart rate was the only haemodynamic change induced by dopexamine (P=0.004, dopexamine group at 85.2+/-9.6 beats/min and placebo group at 71.1+/-7.6 beats/min after 15 min of infusion). CONCLUSION This study demonstrates that administration of dopexamine (1 microg/kg per min) was associated with a significant increase in internal mammary artery graft blood flow with mild increase in heart rate being the only haemodynamic change. Low-dose dopexamine may improve graft flow in the early post CABG period with minimal haemodynamic changes.

Surgical repair of an asymptomatic giant right coronary artery aneurysm.

Background Coronary artery aneurysm (CAA) is a rare finding, being mostly diagnosed on angiography or at autopsies. It is defined as being a dilation of the coronary artery that exceeds the diameter of the patients largest coronary vessel by 1.5 to 2 times. Case Report We describe the operative correction of a giant right CAA measuring in excess of 10 cm. Conclusion Management of giant CAAs is not standardized and surgical strategy remains controversial. In our case, the patient has a successful surgical repair with no postoperative shunts on follow-up investigations.