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Histamine and stress ulcer: New components in organizing a sequential trial on cimetidine prophylaxis in seriously Ill patients and definition of a special group at risk (severe polytrauma)

Histamin und Stressulcus: Neue Strukturen in der Darstellung einer Sequentialstudie über Cimetidinprophylaxe bei Schwerkranken und Definition einer speziellen Risikogruppe

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Zusammenfassung

Bei Patienten der chirurgischen Wach- und Intensivstation wurde eine kontrollierte klinische Studie über den Wert von Cimetidin zur Streßulcusprophylaxe durchgeführt. Die übliche Organisation und Darstellung einer kontrollierten Studie mußte wegen erheblicher theoretischer, ethischer und praktischer Schwierigkeiten bei Planung und Durchführung geändert werden:

  1. (1)

    Zuerst wurde die Untersuchung bei Patienten der Wach- und Intensivstation als randomisierte Doppelblindstudie mit fixem Stichprobenumfang geplant. Ausgeführt wurde eine einfach-blinde Sequentialstudie ausschließlich bei Patienten mit schwerem Polytrauma. Kurz vor Erreichen der vorgegebenen Signifikanzgrenzen wurde sie aus ethischen Gründen abgebrochen und nach Beratung mit einem externen Gutachter mit Hilfe des exakten Testes nach Fisher analysiert (p<0,025).

  2. (2)

    Die notwendigen Informationen über die Studie konnten nicht in einem einzigen Bericht zusammengepreßt werden. Als einer der Teile enthält diese Mitteilung Plan, Klinisches Material, Methoden und Statistik der Studie. Abschnitte über „Theoretische und ethische Aspekte“ und über „Historische Entwicklung der Studie“ wurden eingefügt. Zahlreiche Entscheidungen wurden bereits in Material und Methodik erläutert, um die enorme Komplexität des Entscheidungsprozesses bei klinischen Studien im Gegensatz zu der bei Tierexperimenten hervorzuheben.

  3. (3)

    Um Schlüsse von der Stichprobe auf die Zielpopulation zu erleichtern und Risikogruppen für Streßulkusentstehung zu definieren, wurden alle 6,634 Patienten der Klinik während der Dauer der Studie prospektiv auf klinisch-manifeste Streßläsionen untersucht. Als eines der wichtigsten Merkmale wurde weiterhin die Letalitätsrate für die Gesamtgruppe und für Untergruppen der Traumapatienten in unserer Klinik ermittelt.

Streßulcera traten nur bei Patienten der Wachund Intensivstation auf, vor allem bei Patienten mit schwerem Polytrauma und postoperativen Komplikationen. Cimetidin verhütete sie äußerst wirksam beim schwer Polytraumatisierten. Es ist aber unnötig, das Arzneimittel über die Wach- und Intensivstation auszustreuen wie aus einem Füllhorn des Glücks.

Summary

In patients in a surgical intensive care unit a controlled clinical trial was performed concerned with the pathophysiological functions of histamine in stress ulcer disease and with the influence of cimetidine prophylaxis on this complication. The commonly used organization of a controlled clinical trial was enforced to be changed by considerable theoretical, ethical and practical difficulties in designing and conducting the study:

  1. (1)

    Initially the trial was planned as randomized double-blind using a fixed sample size of patients obtained from the intensive care unit. It was executed as a sequential single-blind study only in patients with severe polytrauma. For ethical reasons it was stopped before the bounderies were reached and was analysed according to the advice of an external referee using Fisher's exact test (p<0.025).

  2. (2)

    The necessary informations about the trial could not be compressed to one single report. As one of several parts this article mainly deals with Design, Clinical materials, Methods and Statistics of the whole investigation. Distinctive sections on Theoretical and Ethical issues and on Historical development of the study were included. Numerous decisions were explained already in Materials and Methods to emphasize the enormous complexity of the decision process in clinical trials in contrast to that in most of the animal experiments.

  3. (3)

    In order to facilitate conclusions from our sample to the target population and to define subgroups of patients with a high risk for stress ulceration all 6,634 patients hospitalized in the Surgery Clinic during the time of the study were prospectively investigated for clinically manifest stress ulceration. Furthermore as one of the most important attributes the lethality rate was calculated for the whole group and various subgroups of trauma patients in our hospital.

As a surprising and remarkable result of the study clinically manifest stress ulcers occurred exclusively in our patients in the intensive care unit and among them mainly in those with severy polytrauma and postoperative complications. Cimetidine was highly effective in preventing stress ulceration in severe polytrauma patients. But it seems absolutely unnecessary to distribute this drug in all patients of a surgical intensive care unit like from a cornucopia of happiness.

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  1. Divisions of Experimental and General Surgery, Department of Operative Medicine I, University of Marburg (Lahn), Germany

    W. Lorenz, M. Fischer, H. Rohde, H. Troidl, H. J. Reimann & Ch. Ohmann

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  2. M. Fischer
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  3. H. Rohde
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  4. H. Troidl
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  5. H. J. Reimann
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  6. Ch. Ohmann
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Supported by a grant from Deutsche Forschungsgemeinschaft (SFB 122, D5)

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Lorenz, W., Fischer, M., Rohde, H. et al. Histamine and stress ulcer: New components in organizing a sequential trial on cimetidine prophylaxis in seriously Ill patients and definition of a special group at risk (severe polytrauma). Klin Wochenschr 58, 653–665 (1980). https://doi.org/10.1007/BF01478603

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  • DOI: https://doi.org/10.1007/BF01478603

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