Search Results

You are looking at 1 - 2 of 2 items for

  • Author or Editor: John D. Pickard x
  • Refine by Access: all x
  • By Author: Iannotti, Fausto x
Clear All Modify Search
Restricted access

James D. Palmer, John L. Francis, John D. Pickard, and Fausto Iannotti

Object. The aim of this study was to determine the safety and efficacy of prophylactic high-dose intravenous aprotinin in reducing intraoperative blood loss in the neurosurgical population.

Methods. A randomized, double-blind, placebo-controlled trial was conducted in parallel groups in two regional neurosurgical departments. One hundred patients with a preoperative diagnosis of intracranial meningioma or vestibular schwannoma subsequently confirmed on histological studies were included. All patients were older than 18 years of age, pregnancy had been excluded, there was no history of bleeding diathesis, no previous exposure to aprotinin, and no ingestion of antiplatelet or anticoagulant medications within the 2 weeks preceding surgery. Aprotinin was administered in doses of 30,000 kallikrein-inhibiting units (KIU)/kg body weight on induction of anesthesia and was continued as an infusion of 10,000 KIU/kg/hr until surgery was complete, or for a maximum of 8 hours. Intraoperative blood loss, blood transfusion, the Glasgow Outcome Scale score, and the Index of Independence were measured, and screening for deep vein thrombosis and the Mini-Mental State Examination were performed.

Conclusions. Intraoperative blood loss was reduced from 1014 ml (geometric mean) to 508 ml (p = 0.028). Although this study was not designed to evaluate the need for blood transfusion, 37 U of blood was used in 11 patients in the aprotinin group and 58 U in 13 patients in the placebo group (not significant). There were no significant differences in postoperative thrombotic risk or other outcome measures between treatment groups. Aprotinin therefore can be safely used to reduce intraoperative blood loss in patients who are not receiving anticoagulation therapy.

Restricted access

Lawrence F. Marshall, Andrew I. R. Maas, Sharon Bowers Marshall, Albino Bricolo, Michael Fearnside, Fausto Iannotti, Melville R. Klauber, Jacques Lagarrigue, Ramiro Lobato, Lennart Persson, John D. Pickard, Jürgen Piek, Franco Servadei, Georgios N. Wellis, Gabrielle F. Morris, Eugene D. Means, and Bruno Musch

Object. The authors prospectively studied the efficacy of tirilazad mesylate, a novel aminosteroid, in humans with head injuries.

Methods. A cohort of 1120 head-injured patients received at least one dose of study medication (tirilazad or placebo). Eighty-five percent (957) of the patients had suffered a severe head injury (Glasgow Coma Scale [GCS] score 4–8) and 15% (163) had sustained a moderate head injury (GCS score 9–12). Six-month outcomes for the tirilazad- and placebo-treated groups for the Glasgow Outcome Scale categories of both good recovery and death showed no significant difference (good recovery in the tirilazad-treated group was 39% compared with the placebo group in which it was 42% [p = 0.461]; death in the tirilazad-treated group occurred in 26% of patients compared with the placebo group, in which it occurred in 25% [p = 0.750]). Subgroup analysis suggested that tirilazad mesylate may be effective in reducing mortality rates in males suffering from severe head injury with accompanying traumatic subarachnoid hemorrhage (death in the tirilazad-treated group occurred in 34% of patients; in the placebo group it occurred in 43% [p = 0.026]). No significant differences in frequency or types of serious adverse events were shown between the treatment and placebo groups.

Conclusions. Striking problems with imbalance concerning basic prognostic variables were observed in spite of the large population studied. These imbalances concerned pretreatment hypotension, pretreatment hypoxia, and the incidence of epidural hematomas. In future trials of pharmacological therapy for severe head injury, serious consideration must be given to alternative randomization strategies. Given the heterogeneous nature of head injury and the identification of populations that do relatively well with standard therapy, target populations with a higher risk for mortality and morbidity may be more suitable for clinical trials of such agents.