Tomi T. Niemi

Gelatin and hydroxyethyl starch, but not albumin, impair hemostasis after cardiac surgery.

We investigated the effect of postoperative administration of colloids on hemostasis in 45 patients after cardiac surgery. Patients were randomized to receive 15 mL kg−1 of either 4% albumin, 4% succinylated gelatin, or 6% hydroxyethyl starch (molecular weight of 200 kDa/degree of substitution 0.5) as a short-term infusion. There was a comparable decrease in maximum clot firmness of thromboelastometry tracings in gelatin and hydroxyethyl starch groups immediately after completion of the infusion, whereas these values remained unchanged in the albumin group. The impairment in clot strength persisted up to 2 h, although the values partly recovered. Postoperative bleeding correlated inversely with the clot strength in pooled data of the artificial colloids. Fibrin formation (clot formation time, &agr;-angle) and fibrinogen-dependent clot strength (maximum clot firmness and shear elastic modulus) were more disturbed in the hydroxyethyl starch group than in the gelatin group. We conclude that after cardiopulmonary bypass surgery, both gelatin and hydroxyethyl starch impair clot strength and fibrin buildup, which may predispose patients to increased blood loss. The greatest impairment in hemostasis was seen after hydroxyethyl starch administration, whereas albumin appeared to have the least effect on hemostatic variables.

Rapidly Degradable Hydroxyethyl Starch Solutions Impair Blood Coagulation After Cardiac Surgery : A Prospective Randomized Trial

BACKGROUND: There is continuing concern about the effect of hydroxyethyl starch (HES) solutions on blood coagulation. Rapidly degradable HES solutions with more favorable effects on clot strength have therefore been developed. Because the risk of bleeding is increased after cardiopulmonary bypass, we examined whether these types of HES solutions could be administered after cardiac surgery without an alteration of coagulation. METHODS: Two new rapidly degradable HES solutions were compared with human albumin in 45 patients scheduled for elective primary cardiac surgery. After admission to the cardiac surgical intensive care unit, the patients were allocated in random order to receive either 15 mL/kg of HES solution with low molecular weight and low molar substitution (either 6% HES200/0.5 or 6% HES130/0.4) or 4% human albumin solution as a short-time (70–240 min) infusion. RESULTS: Clot formation time was prolonged and maximum clot firmness was decreased in thromboelastometry tracings after infusion of both HES solutions. This impairment in thromboelastometry tracings partly recovered (using InTEM® and ExTEM® coagulation activators) at 2 h after the completion of the study infusion. Platelet contribution to maximum clot firmness remained unaffected in all of the study groups. HES did not induce fibrinolysis. No changes in thromboelastometry tracings were observed after human albumin infusion. Chest tube drainage was comparable in the study groups. CONCLUSIONS: We conclude that a short-time infusion of rapidly degradable HES solutions after cardiac surgery produces impairment in fibrin formation and clot strength in thromboelastometry tracings. In this clinical setting, human albumin does not impair hemostasis.

Hydroxyethylstarch and gelatin solutions impair blood coagulation after cardiac surgery: a prospective randomized trial

BACKGROUND Colloids are often used after cardiac surgery as intravascular volume replacement therapy. Cardiac surgical patients have an increased risk of bleeding. Both hydroxyethylstarch (HES) and gelatin solutions impair haemostasis. We examined the impact and dose effect on coagulation of HES 130/0.4, gelatin, or Ringers acetate solutions after cardiac surgery. METHODS Forty-five patients received three boluses (each 7 ml kg(-1)) of either 6% HES 130/0.4, 4% gelatin, or Ringers acetate solution after elective cardiac surgery. The infusion of study solution was continued in the dose 7 ml kg(-1) over the following 12 h. The total dose of study solution was 28 ml kg(-1). Hypovolaemia was treated with Ringers acetate. Modified thromboelastometry was performed to detect coagulation disorders. RESULTS Clot formation time was prolonged and clot strength decreased after infusion of 7, 14, and 21 ml kg(-1) of either colloid compared with the Ringers acetate group. After infusion of 14 and 21 ml kg(-1) of Ringers acetate, clot strength was slightly, but significantly, increased. On the first postoperative morning, clot strength was still decreased in the gelatin group in comparison with the Ringers acetate group. Neither HES nor gelatin induced fibrinolysis. Chest tube drainage was comparable between all groups. CONCLUSIONS Even a small dose of HES 130/0.4 or gelatin impaired clot strength after cardiac surgery in a dose-dependent fashion, but neither colloid increased blood loss.

Thromboelastometry in patients with severe sepsis and disseminated intravascular coagulation

Severe sepsis induces coagulopathy, which may lead to disseminated intravascular coagulation (DIC). Thromboelastometry is a point-of-care whole blood coagulation monitor, which has been validated in human endotoxemia model. We assessed thromboelastometry in severe sepsis and overt DIC and investigated its applicability in differentiating sepsis-related coagulation disturbances. Thromboelastometry (EXTEM and FIBTEM tests) and traditional coagulation assays were analyzed in 28 patients with severe sepsis, 12 of who fulfilled the criteria of overt DIC on admission. Ten healthy persons served as controls. Coagulation parameters, clotting time, clot formation time (CFT), α angle, maximal clot firmness (MCF) and lysis index at 60 min, were registered. In patients with overt DIC, EXTEM MCF, CFT and α angle differed from that in both healthy controls and patients without DIC, indicating hypocoagulation (MCF 52, 63 and 68 mm; CFT 184, 88 and 73 s; and α angle 58, 72 and 76°, respectively, P < 0.01 for all). In patients without DIC, the trend was toward hypercoagulation in EXTEM and FIBTEM MCF (68 vs. 63 mm, P = 0.042 and 23 vs. 15 mm, P = 0.034, respectively). Receiver operating characteristic curves showed that MCF, CFT and α angle discriminated patients with overt DIC moderately (area under curve 0.891, 0.815 and 0.828, respectively, P < 0.001 for all). Traditional coagulation assays showed progressively worsening coagulopathy from controls to septic patients without DIC and further to those with overt DIC. We conclude that thromboelastometry may be a valuable tool in assessing whole blood coagulation capacity in patients with severe sepsis with and without overt DIC.

N-acetylcysteine for the prevention of kidney injury in abdominal aortic surgery: a randomized, double-blind, placebo-controlled trial.

In this prospective, randomized, placebo-controlled, double-blind trial we studied the effects of IV N-acetylcysteine for prevention of renal injury in patients undergoing abdominal aortic surgery. Seventy patients without previously documented renal dysfunction were randomly allocated to receive either N-acetylcysteine (150 mg/kg mixed in 250 mL of 5% dextrose infused in 20 min, followed by an infusion of 150 mg/kg in 250 mL of 5% dextrose over 24 h) or placebo. The infusion was started after the induction of anesthesia. The primary outcome measure was renal injury as measured by the increases in urinary N-acetyl-β-d-glucosaminidase (NAG)/creatinine ratio (indicator of renal tubular injury) and urinary albumin/creatinine ratio (indicator of glomerular injury). Renal function was assessed by measuring plasma creatinine and serum cystatin C concentrations. The urinary NAG/creatinine ratio increased significantly from baseline to before crossclamp and remained increased on day 5 in both groups. The urinary albumin/creatinine ratio increased significantly from baseline to 6 h after declamping in the N-acetylcysteine group. However, the changes in the NAG/creatinine ratio and the albumin/creatinine ratio were not significantly different between the two groups. Plasma creatinine and serum cystatin C values remained unchanged during the study period in both groups. In conclusion, N-acetylcysteine did not offer any significant protection from renal injury during elective aortic operation in patients with normal preoperative renal function, and some degree of tubular injury seems to occur before aortic crossclamp.

The effect of N-acetylcysteine on blood coagulation and platelet function in patients undergoing open repair of abdominal aortic aneurysm

N-acetylcysteine (NAC) may offer renal and hepatic protection during surgery, but in experimental studies it has been shown to impair coagulation. Since very little is known about the effects of NAC on blood coagulation in surgical patients, we studied its effects during abdominal aortic reconstruction. NAC (a bolus of 150 mg/kg followed by a continuous 24-h infusion of 150 mg/kg) or the same volume of placebo was given intravenously, in a randomized double-blinded fashion, to 20 patients undergoing abdominal aortic aneurysm repair. The haematocrit, platelet count, prothrombin time, thromboelastometry, and platelet aggregation were studied during and after surgery. Total blood loss was also measured. The median (25th–75th percentiles) decrease of the prothrombin time value was 33.0% (30–37%) after NAC treatment and 6.5% (4–8%) after placebo (P < 0.001). Postoperative prothrombin time values remained lower in the patients receiving NAC. In thromboelastometry tracings the coagulation time was more prolonged after the bolus of NAC (P = 0.02). Platelet aggregation induced with adenosine diphosphate decreased after NAC but not after placebo. Low prothrombin time values before and after bolus infusions were associated with increased blood loss (P = 0.008 and P = 0.015, respectively). NAC has anticoagulant and platelet-inhibiting properties in patients undergoing major vascular surgery. This abnormal haemostatic activity should be considered when NAC is administered to patients with increased bleeding risk.

Colloid solutions: a clinical update

Albumin, dextran, gelatin, and hydroxyethyl starch (HES) solutions are colloids that efficiently expand the circulating blood volume. The administration of colloids restores the intravascular volume with minimal risk of tissue edema in comparison with crystalloid solutions alone. However, colloids are always given for surgical and critically ill patients. The type of the colloid, volumes applied, aggressiveness of fluid resuscitation, and the volume status at the initial phase of administration determine their clinical responses. The outcome after fluid resuscitation with various colloids in critically ill patients seems to be comparable according to systematic reviews. A randomized, adequately powered clinical trial comparing modern nonprotein colloid to albumin is still lacking. Rapidly degradable HES solutions have good hemodynamic effects, and the risk of adverse renal and coagulation effects, as well as allergic reactions, is minimal. The current investigation has also shown the beneficial effect of HES solution (especially HES 130/0.4) on inflammatory response, postoperative nausea and vomiting, and postoperative outcome. The indication of colloids with an assessment of the degree of hypovolemia and safety profiles should thus be taken into consideration before colloid administration.

Haemostatic disturbances in burned patients during early excision and skin grafting

Bleeding is a major problem during early excision of burned skin. Therefore, 13 severely burned adult patients operated on during the first week after the trauma were studied. Blood loss was replaced with crystalloids, colloids and packed red cell concentrates (PRC). After ten infused PRCs, four fresh frozen plasma (FFP) units were given and thereafter one FFP unit with one PRC unit. Arterial blood samples were drawn before anaesthesia (SO), during operation after every four units of PRC transfusion (S1-4), 4 h postoperatively (S5) and on the first postoperative morning (S6). Prothrombin time (%) and activated partial thromboplastin time (s) were abnormal before operation (median values 67%, range 22-99% and 44 s, range 30-86 s, respectively). Prothrombin time decreased during operation and reached the critical level for normal haemostasis at S2. Thrombelastography showed decreased clot formation rate and impaired fibrin platelet interaction peri- and postoperatively. Fibrinogen and factor VIII activity were high preoperatively (median 6.1 g/l and 253%) and the critical values for normal haemostasis were not reached. Burned patients have a consumption coagulopathy which, in combination with haemodilution during operation, results in a clinically significant deficiency of coagulation factors II, VII and X, in spite of reactive elevation of coagulation factor VIII and fibrinogen.

Haemodynamics and acid-base equilibrium after cardiac surgery: comparison of rapidly degradable hydroxyethyl starch solutions and albumin.

Background: Stable haemodynamics is often achieved by administration of colloids after cardiac surgery. We conducted a prospective, randomized, open-label study comparing haemodynamics and acid-base equilibrium after infusion of two rapidly degradable hydroxyethyl starch (HES) solutions or human albumin (HA) to cardiac surgical patients. Materials and Methods: 45 patients received a predetermined fixed dose of 15 ml kg−1 of either 6% HES (MW 130 kDa, n=15), 6% HES (MW 200 kDa, n=15) or 4% HA (MW 69 kDa, n=15) after on-pump cardiac surgery. Results: Left ventricular filling pressures assessed using pulmonary artery catheter responded similarly in all groups. Mean (SD) cardiac index was higher in HES130 [3.5 1 min−1 m−2 (0.7)] and HES200 [3.5 1 min−1 m−2 (0.5)] than in HA [2.8 1 min−1 m−2 (0.6)] group after completion of infusion (P=0.002) but no differences were detected at 2 and 18 hours. Oxygen delivery increased in both HES groups but not in HA group. After cessation of infusion base excess was the most negative in HA group. At 2 hours mean (SD) base excess was higher in HWS130 [0 (1.32)] than in HES200 [-1.32 (2.27)] and HA [-2.3 (1.3)] group (P=0.002, between the groups). Conclusions: We conclude that the effect of albumin on cardiac performance is inferior than that of HES130 or HES200 in early postoperative phase after cardiac surgery. HES130 induces no alterations in acid-base equilibrium whereas a negative base excess was observed after HA infusion.

Preoperative identification of neurosurgery patients with a high risk of in-hospital complications: a prospective cohort of 418 consecutive elective craniotomy patients.

OBJECT Patients undergoing craniotomy are routinely assessed preoperatively, yet the role of these assessments in predicting outcome is poorly studied. This study aimed to identify preoperative factors predicting in-hospital outcome after cranial neurosurgery. METHODS The study cohort consisted of 418 consecutive adults undergoing elective craniotomy for any intracranial lesion. Apart from the age criteria (≥ 18 years), almost all patients were considered eligible for the study to increase external validity of the results. The studied preoperative assessments included various patient-related data, routine blood tests, American Society of Anesthesiologists (ASA) Physical Status Classification system, and a local modification of the ASA classification (Helsinki ASA classification). Adverse outcomes were in-hospital mortality, in-hospital systemic or infectious complications, and in-hospital CNS deficits. Resource use was defined as length of stay (LOS) in the intensive care unit and overall LOS in the hospital. RESULTS The in-hospital mortality rate was 1.0%. In-hospital systemic or infectious complications and permanent or transient CNS deficits occurred in 6.7% and 11.2% of the patients, respectively. Advanced age (≥ 60-65 years), elevated C-reactive protein level (> 3 mg/L), and high Helsinki ASA score (Class 4) were associated with in-hospital systemic and infectious complications, and a combination of these could identify one-fourth of the patients with postoperative complications. Moreover, this combination of preoperative assessment parameters was significantly associated with increased resource use. CONCLUSIONS In this first prospective and unselected cohort study of outcome after elective craniotomy, simple preoperative assessments identified patients with a high risk of in-hospital systemic or infectious complications as well as extended resource use. Presented risk assessment methods may be widely applicable, also in low-volume centers, as they are based on composite predictors and outcome events.