Histamine Release in Human Subjects by Modified Gelatin (Haemaccel) and Dextran: An Explanation for Anaphylactoid Reactions Observed Under Clinical Conditions?

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.

Definition and classification of the histamine-release response to drugs in anaesthesia and surgery: Studies in the conscious human subject

“…Before reliable and practicable [20] histamine assays in human plasma became available for routine use [4,26,27] a histamine-release response to drugs could not be estimated in clinical conditions with an acceptable accuracy [9,10,28,29,34,36,45,51,58,62]. But even one decade after the discovery of H2-receptor antagonists [5] and the development of these highly sensitive and specific asays [4,26] histamine was still not generally recognized as an important mediator of any pathological and clinical phenomenon [63].…”

“…A dose was chosen which increased the plasma histamine levels to such an extent as the average histamine-release response to drugs used in anaesthesia [28,34]. In addition, the same subjects received one of the "clinical" histamine releasers, polygeline (Haemaccel) [29,34,39,40) a short time after exogenous histamine. From all the findings a questionnaire with many items was developed to diagnose an average histamine-release response.…”

“…Polygeline was tested in a dose of 500 ml/3 rain in normovolaemic haemodiluation [34] since this design repeatedly has produced average histamine-release responses [28,[33][34][35]54]. Hae-maccel as a plasma substitute was pure and chemically defined and could be administered in clinical conditions where no other drug, solvent or treatment interferes [34].…”

“…Hae-maccel as a plasma substitute was pure and chemically defined and could be administered in clinical conditions where no other drug, solvent or treatment interferes [34]. Histamine release by this drug was predominant [13,35] i.e.…”

Anti H1- and anti H2-premedication

“…In the test group receiving the H Iand HE-blockade, seven volunteers released histamine to greater levels than in the control group, including two subjects with plasma histamine concentrations of 5 ng • m1-1, at the top of the Bateman curve. Since in all previous studies (see especially [5,7]), increasing plasma histamine levels to this order of magnitude always caused anaphylactoid reactions of a considerable severity, the complete prevention of any clinical signs and cardiovascular reactions in these subjects was very remarkable. The result of this trial justified the definition of histamine release as predominant in the adverse reaction to polygeline [2].…”