Volume replacement with a balanced hydroxyethyl starch (HES) preparation in cardiac surgery patients.

OBJECTIVE: Balanced fluids appear to be have advantages over unbalanced fluids for correcting hypovolemia. The effects of a new balanced hydroxyethyl starch (HES) were studied in cardiac surgery patients. DESIGN: Prospective, randomized, unblinded study. SETTING: Clinical study in a single cardiac surgery institution. PARTICIPANTS: Sixty patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTION: Patients received either a balanced 6% HES 130/0.4 plus a balanced crystalloid (n = 30) or an unbalanced HES-in-saline plus saline (n = 30) to keep cardiac index >2.5 L/min/m(2). MEASUREMENTS AND MAIN RESULTS: Base excess (BE), kidney function, inflammatory response (interleukins-6, -10), endothelial activation (intercellular adhesion molecule-1 [ICAM]), and coagulation (thromboelastometry, whole blood aggregation) were measured after induction of anesthesia, after surgery and 5 hours later, and at the 1st and 2nd postoperative days; 2,950 +/- 530 mL of balanced and 3,050 +/- 560 mL of unbalanced HES were given. BE was reduced significantly in the unbalanced group (from 1.11 +/- 0.71 mmol/L to -5.11 +/- 0.48 mmol/L after surgery) and remained unchanged in the balanced group. Balanced volume replacement resulted in significantly lower IL-6, IL-10, and ICAM plasma concentrations and lower urine concentrations of kidney-specific proteins than in the unbalanced group. After surgery, thromboelastometry data and platelet function were changed significantly in both groups; 5 hours thereafter they were significantly changed only in the unbalanced group. CONCLUSION: A plasma-adapted HES preparation in addition to a balanced crystalloid resulted in significantly less decline in BE, less increase in concentrations of kidney-specific proteins, less inflammatory response and endothelial damage, and fewer changes in hemostasis compared with an unbalanced fluid strategy.

Cardiopulmonary bypass priming using a high dose of a balanced hydroxyethyl starch versus an albumin-based priming strategy.

BACKGROUND: The optimal priming solution for cardiopulmonary bypass (CPB) is unclear. In this study, we evaluated the influence of high-volume priming with a modern balanced hydroxyethyl starch (HES) preparation on coagulation, inflammation, and organ function compared with an albumin-based CPB priming regimen. METHODS: In 50 patients undergoing coronary artery bypass grafting, the CPB circuit was prospectively and randomly primed with either 1500 mL of 6% HES 130/0.42 in a balanced electrolyte solution (Na(+) 140 mmol/L, Cl(-) 118 mmol/L, K(+) 4 mmol/L, Ca(2+) 2.5 mmol/L, Mg(++) 1 mmol/L, acetate(-) 24 mmol/L, malate(-) 5 mmol/L) (n = 25) or with 500 mL of 5% human albumin plus 1000 mL 0.9% saline solution (n = 25). Inflammation (interleukins [IL]-6, -10), endothelial damage (soluble intercellular adhesion molecule-1), kidney function (kidney-specific proteins alpha-glutathione S-transferase, neutrophil gelatinase-associated lipocalin), coagulation (measured by thrombelastometry [ROTEM, Pentapharm, Munich, Germany]), and platelet function (measured by whole blood aggregometry [Multiplate analyzer, Dynabyte Medical, Munich, Germany]) were assessed after induction of anesthesia, immediately after surgery, 5 h after surgery, and on the morning of first and second postoperative days. RESULTS: Total volume given during and after CPB was 3090 +/- 540 mL of balanced HES and 3110 +/- 450 mL of albumin. Base excess after surgery was lower in the albumin-based priming group than in the balanced HES priming group (-5.9 +/- 1.2 mmol/L vs +0.2 +/- 0.2 mmol/L, P = 0.0003). Plasma levels of IL-6, IL-10, and intercellular adhesion molecule-1 were higher after CPB in the albumin-based priming group compared with the HES priming group at all time periods (P = 0.0002). Urinary concentrations of alpha-glutathione S-transferase and neutrophil gelatinase-associated lipocalin were higher after CPB through the end of the study in the albumin group compared with the balanced HES group (P = 0.00004). After surgery through the first postoperative day, thrombelastometry data (clotting time and clot formation time) revealed more impaired coagulation in the albumin-based priming group compared with the HES priming group (P = 0.004). Compared with baseline, platelet function was unchanged in the high-dose balanced HES priming group after CPB and 5 h after surgery, but it was significantly reduced in the albumin-based priming group. CONCLUSION: High-volume priming of the CPB circuit with a modern balanced HES solution resulted in reduced inflammation, less endothelial damage, and fewer alterations in renal tubular integrity compared with an albumin-based priming. Coagulation including platelet function was better preserved with high-dose balanced HES CPB priming compared with albumin-based CPB priming.

Does coagulation differ between elderly and younger patients undergoing cardiac surgery?

OBJECTIVE: Multiple improvements allow cardiac surgery in an increasingly older population. It is still unclear whether perioperative hemostasis differs between elderly and younger patients. DESIGN: Prospective, observational study. SETTING: Single institutional study at an urban, university-affiliated hospital. PATIENTS: Twenty-one consecutive patients aged over 80 years and 21 consecutive patients aged under 60 years undergoing first-time elective aortocoronary bypass grafting. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Modified thromboelastography (TEG) using different activators [intrinsic TEG (InTEG); extrinsic TEG (ExTEG); fibrinogen TEG (fibTEG)] was carried out to measure coagulation time [CT = reaction time (r)], clot formation time [CFT = coagulation time (k)], and maximum clot firmness [MCF = maximal amplitude (MA)]. Measurements were performed before surgery, at the end and 5 h after surgery on the intensive care unit (ICU), and on the morning of the 1st postoperative day (POD). Blood loss was slightly higher in the elderly than in the younger patients. Most TEG data were already significantly different between elderly and younger patients at baseline, indicating altered coagulation in the elderly prior to surgery (hypocoagulability). After surgery and on the ICU, elderly patients showed similar alterations in TEG to those of the younger patients (e.g. InTEG-CT: from 183+/-21 to 239+/-28 s versus from 146+/-15 to 186+/-26 s). On the 1st POD, most TEG data had returned almost to baseline values, however, they were still different between elderly and younger patients. CONCLUSIONS: Elderly cardiac surgery patients already showed moderately altered coagulation prior to surgery. Thus elderly patients may be at risk of developing postoperative alterations in hemostasis on the ICU. The exact reasons for the impaired coagulation in the elderly remains to be determined.

Prophylactic use of the phospodiesterase III inhibitor enoximone in elderly cardiac surgery patients: effect on hemodynamics, inflammation, and markers of organ function.

OBJECTIVE: Elderly patients appear prone to develop overwhelming post-bypass inflammation and organ dysfunction. We assessed the effect of prophylactic administration of the phosphodiesterase III inhibitor enoximone on inflammation and organ function. DESIGN: Prospective, blinded, randomized, placebo-controlled study. SETTING: Clinical investigations on a surgical intensive care unit. PATIENTS: 40 consecutive patients aged over 80 years undergoing first-time coronary artery bypass grafting. INTERVENTIONS: Enoximone was given to 20 patients after induction of anesthesia (initial bolus 0.5 mg/kg) followed by a continuous infusion of 2.5 micro g/kg per minute until the 2nd postoperative day. Control patients ( n=20) received saline solution. MEASUREMENTS AND RESULTS: Interleukins 6, 8, and 10 and soluble adhesion molecules were measured. Liver function was assessed by the monoethylglycine-xylidide test and by measuring alpha-glutathione S-transferase plasma levels; splanchnic perfusion by continuous gastric tonometry; renal function by measuring creatinine and alpha(1)-microglobulin. Interleukins increased significantly more in controls than in the enoximone-pretreated patients. Soluble adhesion molecules were significantly more increased in controls. Liver function was more altered in controls than in the enoximone-pretreated patients. alpha(1)-Microglobulin increased significantly more in controls than in the enoximone group, indicating less tubular damage in the verum group. CONCLUSION: . Prophylactic use of enoximone in cardiac surgery patients aged over 80 years resulted in less post-bypass inflammation and improvement in markers of organ function than in the placebo group. The exact mechanisms by which enoximone exerts its beneficial effects in these patients remains to be elucidated.

The influence of a balanced volume replacement concept on inflammation, endothelial activation, and kidney integrity in elderly cardiac surgery patients.

PURPOSE: A balanced fluid replacement strategy appears to be promising for correcting hypovolemia. The benefits of a balanced fluid replacement regimen were studied in elderly cardiac surgery patients. METHODS: In a randomized clinical trial, 50 patients aged >75 years undergoing cardiac surgery received a balanced 6% HES 130/0.42 plus a balanced crystalloid solution (n = 25) or a non-balanced HES in saline plus saline solution (n = 25) to keep pulmonary capillary wedge pressure/central venous pressure between 12-14 mmHg. Acid-base status, inflammation, endothelial activation (soluble intercellular adhesion molecule-1, kidney integrity (kidney-specific proteins glutathione transferase-alpha; neutrophil gelatinase-associated lipocalin) were studied after induction of anesthesia, 5 h after surgery, 1 and 2 days thereafter. Serum creatinine (sCr) was measured approximately 60 days after discharge. RESULTS: A total of 2,750 +/- 640 mL of balanced and 2,820 +/- 550 mL of unbalanced HES were given until the second POD. Base excess (BE) was significantly reduced in the unbalanced (from +1.21 +/- 0.3 to -4.39 +/- 1.0 mmol L(-1) 5 h after surgery; P < 0.001) and remained unchanged in the balanced group (from 1.04 +/- 0.3 to -0.81 +/- 0.3 mmol L(-1) 5 h after surgery). Evolution of the BE was significantly different. Inflammatory response and endothelial activation were significantly less pronounced in the balanced than the unbalanced group. Concentrations of kidney-specific proteins after surgery indicated less alterations of kidney integrity in the balanced than in the unbalanced group. CONCLUSIONS: A total balanced volume replacement strategy including a balanced HES and a balanced crystalloid solution resulted in moderate beneficial effects on acid-base status, inflammation, endothelial activation, and kidney integrity compared to a conventional unbalanced volume replacement regimen.

Influence of volume therapy with a modern hydroxyethylstarch preparation on kidney function in cardiac surgery patients with compromised renal function: a comparison with human albumin.

OBJECTIVE: There is continuing concern about the influence of hydroxyethylstarch on renal function in patients with compromised kidney function. DESIGN: Prospective, randomized, single-center study. SETTING: University-affiliated hospital. PATIENTS: Fifty patients undergoing elective, first-time coronary artery bypass grafting using cardiopulmonary bypass with a preoperative serum creatinine between 1.5 and 2.5 mg/dL. INTERVENTIONS: According to a prospective, randomized sequence, the patients received either hydroxyethylstarch with a low molecular weight (mean molecular weight 130 kD) and a low molar substitution (0.4) (6% hydroxyethylstarch 130/0.4) (n = 25) or 5% human albumin (n = 25). Volume was added to the priming (500 mL) and given perioperatively until the second postoperative day to keep pulmonary artery occlusion pressure or central venous pressure between 12 and 14 mm Hg. MEASUREMENTS AND MAIN RESULTS: Serum creatinine and cystatin plasma levels were measured from arterial blood samples. From urine specimens, N-acetyl-beta-D-glucosaminidase, glutathione transferase-alpha, and neutrophil gelatinase-associated lipocalin were measured. Measurements were performed after induction of anesthesia, at the end of surgery, 5 hrs after surgery, and on the first and second postoperative days. A follow-up after discharge from the hospital (60 days) was also done. Similar amounts of hydroxyethylstarch and albumin were infused. Serum creatinine, glomerular filtration rate, and cystatin C plasma levels were without significant differences between the groups. Concentrations of kidney-specific proteins were elevated at baseline and increased significantly after surgery without showing group differences. Urinary levels of neutrophil gelatinase-associated lipocalin increased more in the albumin- than in the hydroxyethylstarch-treated patients. None of the patients developed acute renal failure requiring renal replacement therapy during the hospital stay and thereafter. CONCLUSIONS: A hydroxyethylstarch preparation with a low molecular weight and a low molar substitution given in cardiac surgery patients with preoperative compromised kidney function did not negatively influence kidney integrity compared with a human albumin-based volume replacement strategy.

The prophylactic use of the beta-blocker esmolol in combination with phosphodiesterase III inhibitor enoximone in elderly cardiac surgery patients.

We assessed the influence of the prophylactic use of a combination of the IV beta-adrenergic blocker, esmolol, and the phosphodiesterase III inhibitor, enoximone, on postbypass hemodynamic status, inflammation, and endothelial and organ function in a prospective, randomized, placebo-controlled study in 42 patients aged >65 yr undergoing aortocoronary bypass grafting. In 21 patients, esmolol (aim: heart rate <70 bpm) plus enoximone (initial bolus of 0.5 mg/kg followed by a continuous infusion of 2.5 microg x kg(-1) x min(-1)) was started after induction of anesthesia and continued until the morning of the first postoperative day; another 21 patients received saline solution as placebo. Hemodynamics, splanchnic perfusion (gastric-arterial CO(2) gap), liver function (glutathione transferase-alpha plasma levels), renal function (creatinine clearance, urine concentrations of N-acetyl-beta-D-glucosaminidase), myocardial ischemia (creatine-kinase MB and troponin T plasma levels), inflammation (elastase, interleukin-6 and -8 plasma levels), and endothelial integrity (adhesion molecules plasma levels) were assessed at baseline, before and after cardiopulmonary bypass (CPB), and in the intensive care unit until the first postoperative day. Catecholamine requirements were significantly less in the treated than in the nontreated patients. Heart rate was significantly slower, cardiac index was higher, and gastric-arterial CO(2) gap was significantly lower in the treatment group. Troponin T, beta-N-acetyl-beta-D-glucosaminidase, glutathione transferase-alpha, and soluble adhesion molecules increased significantly in the untreated control, but remained almost normal in the esmolol+enoximone patients. Inflammatory responses (elastase/interleukins) were attenuated by esmolol+enoximone. We conclude that, in comparison to an untreated control, the prophylactic use of a combination of esmolol and enoximone in elderly patients undergoing cardiac surgery with cardiopulmonary bypass resulted in overall beneficial effects on postbypass hemodynamic status, organ function, inflammatory response, and endothelial integrity.