Haemaccel

Abstract: Objective To compare the efficacy of crystalloid (Normal saline) and colloid (polymer from degraded Gelatin in saline Haemaccel) intravenous fluid in restoration of circulating volume in children with septic shock. Design Prospective, randomized, open-label trial. Setting Pediatric Emergency and Intensive Care Unit of a tertiary care referral and teaching hospital. SUBJECTS AND INCLUSION CRITERIA: Sixty patients, between 1 month to 12 years of age, with septic shock, without clinical evidence of organ failure at admission or underlying immunodeficiency. Intervention Resuscitation with normal saline or polymer from degraded gelatin (Haemaccel) in the boluses rate of 20 mL/kg till hemodynamic stabilization or if central venous pressure (CVP) exceeded 10 mmHg (fluid requirement beyond 40 mL/kg guided by BP and CVP). Methods Hemodynamic parameters (heart rate, capillary filling time, pulse volume, and blood pressure) were recorded before and during resuscitation, and then 2 hourly for 12 hours. Central venous pressure line was placed within first hour, soon after starting fluids. Estimation of plasma volume and body water was done at the end of first hour of fluid resuscitation. Outcome measures Hemodynamic stabilization (heart rate, capillary refill time, systolic BP in normal range), plasma volume at the end of fluid resuscitation and incidence of organ dysfunction. Results 31 patients were randomized to normal saline and 29 to gelatin polymer. Both the groups were similar with respect to age, gender, primary diagnosis, initial hemodynamic parameters and PRISM score. Pneumonia (n = 22; 36%), gut-associated sepsis (n = 13), and dengue hemorrhagic fever (n = 11) were the common primary diagnosis. Initial hemodynamic stabilization was achieved in all. The mean (SD plasma volume (saline--53.4 (2.0 mL/kg, gelatin polymer--53.2 (1.9 mL/kg), extracellular fluid volume, total body water and interstitial fluid volume at the end of first hour of resuscitation were similar. The requirement of inotropes, incidence of organ dysfunction and case fatality rate (Saline--29%, gelatin polymer--31%), were similar in two groups. Conclusion Both normal saline and gelatin polymer solution were equally effective as resuscitation fluid with respect to restoration of plasma volume and hemodynamic stability. Normal saline upto 110 mL/kg, and gelatin polymer solution upto 70 mL/kg may be required in first hour for successful fluid resuscitation of septic shock in children.

Abstract: Histamine release by modified gelatin (Haemaccel) and dextran (Macrodex) has been demonstrated in volunteers by direct and indirect methods. In a pilot study of Haemaccel, histamine release was observed in six of seven volunteers. The highest plasma histamine concentration was 4.8 ng/ml, the lowest 1.7 ng/ml: two of the subjects showed slight allergic reactions. Using Haemaccel batch 2551, 10 out of 12 subjects reacted to the rapid infusion of Haemaccel with increased plasma histamine concentrations, whereas none reacted to Ringer's solution. None of the 10 subjects had an allergic reaction, but an increase in gastric secretion was observed in eight. Changes in the venous basophil granulocyte count were found in both those who reacted and those who did not react to Haemaccel. After the rapid infusion of dextran the highest plasma histamine concentration was 5.0 ng/ml, the lowest 1.3 ng/ml. The withdrawal of blood had no influence on plasma histamine concentration. The incidences of histamine release produced by Haemaccel varied with different batches. Thus, it seems unlikely that immunological mechanisms are principally responsible. Nine instances of allergic and anaphylactoid reactions to plasma substitutes have been reported, seven after Haemaccel infusion, and two after dextran administration. One of the patients who received dextran died. Histamine release was always associated with Haemaccel infusion and corresponded in extent to the clinical symptoms observed, but there was no significant histamine release associated with the reactions to dextran.

Abstract: Histamine release by drugs used in anaesthesia and surgery has been often demonstrated in human volunteers, but only occasionally in patients. Three questions arose from these studies. (1) Is the incidence of histamine release high in patients during routine anaesthesia and surgery? (2) Can the clinical effects of histamine release in man be prevented by H1+H2-receptor antagonists? (3) Are there any side-effects of such a premedication? These problems were investigated in patients and volunteers by randomized controlled clinical trials using only one of the histamine-liberating drugs in man, the plasma substitute Haemaccel. This drug was chosen because it causes a reproducible histamine release in man and because its mechanism of action in man is largely known. (1) Out of 600 orthopaedic patients 30 (5%) showed anaphylactoid reactions following Haemaccel infusion. 26 of these had a histamine release of more than 1 ng histamine/ml plasma. Using predictive values this gives an efficiency of the test by nearly 98%. (2) In volunteers the combination of an H1-plus H2-receptor antagonist (dimethpyrindene and cimetidine) completely prevented the clinical effects of histamine release by Haemaccel (9 allergoid and anaphylactoid reactions in the control group, none in the H1+H2-group). The incidence of histamine release, however, remained unchanged. (3) The premedication was found to release histamine itself. Cimetidine was effective when given alone but especially in combination with chlorpheniramine (4 events out of 7 applications). The clinical side-effects of these premedication were mild since apparently the free histamine was largely blocked at the receptor sites.

Abstract: The rational choice of a plasma substitute for states of hypovolaemia depends partly on its colloid osmotic pressure (COP). We have measured the COP of 108 samples of plasma substitute across selectively permeable membranes which retain molecules greater than 10000 dalton (COP10) and 50000 dalton (COP50) the ratio COP50/COP10 providing a potential index of diffusibility of the smaller molecules across capillary membranes. 6% Hespan solution showed a particularly favourable COP50/COP10 ratio at 0.58 indicating a potential for good retention in the circulation whilst 3.5% Haemaccel showed a COP50/COP10 ratio of 0.18 indicating a potential for marked transcapillary diffusion, especially in states of capillary leak. In patients with normal capillary permeability both Gelofusine and Dextran 110 are likely to show adequate retention in the circulation with a COP50/COP10 ratio of 0.37 and 0.39 respectively. These are comparable to the retention of 4.5% human albumin (0.36) but all of the plasma substitutes tested, with the exception of Haemaccel, provided a higher COP across both membranes than 4.5% human albumin solution. An in vivo comparison of these plasma substitutes is required to confirm the advantages of macromolecular colloids in states of capillary leak.