The Natural Half Life of a Large Stock of Reusable Laryngeal Mask Airways at a Teaching Hospital

Neff et al. (1) describe a randomized trial of 31 craniocerebral trauma patients receiving repetitive infusions over a maximum of 28 d of either hydroxyethyl starch (HES) 130/0.4 up to 70 mL · kg 1 · d 1 or HES 200/0.5 up to 33 mL · kg 1 · d . Albumin was administered for additional intravascular volume needed in the HES 200/0.5 group. Patients with a history of coagulation disorders, chronic renal insufficiency, severe liver insufficiency, or cardiac insufficiency were excluded. The investigational plan of Neff et al. was to enroll 40 patients. Of 128 patients screened, 95 failed to meet the enrollment criteria, and two could not be enrolled for logistic reasons. After 31 patients had been enrolled, the institutional ethics committee raised questions regarding the occurrence of intracranial bleeding complications in both groups and requested an interim analysis. Intracranial bleeding complications occurred in 31% of the HES 130/0.4 group and 33% of HES 200/0.5 recipients. The investigators stated, without providing evidence, that the intracranial bleeding complications “were related to the underlying cerebral trauma and were not accompanied by coagulation disorders. ” They further indicated that the trial was not resumed after the interim analysis because of more frequent episodes of elevated intracerebral pressure in the control group, which they speculated may have been attributable to the cumulative 7 L of albumin administered in this group rather than the 22 L of HES 200/0.5. They did not, however, acknowledge two randomized trials (2,3) and a prospective clinical outcome study (4) providing evidence that albumin improves outcomes of brain injury. Nor did they mention coagulation abnormalities due to HES 200/0.5 demonstrated in one randomized (5) and two nonrandomized (6,7) controlled trials of patients with cerebrovascular diseases. They also did not cite a pharmacovigilance study documenting 9 cases of acquired type I von Willebrand’s disease associated with HES 200/0.5 administered to patients with subarachnoid hemorrhage (8). Four of the cases were complicated by cerebral hemorrhage and one by extradural hematoma. Three of the four cerebral hemorrhage cases were fatal. No significant between-group differences were detected by Neff et al. in blood loss, use of blood products, or neurological outcomes at up to 6 mo. Factor VIII and von Willebrand factor antigen and ristocetin cofactor were transiently and modestly higher in the HES 130/0.4 group; however, these observations may have been due to the higher mean daily volume of fresh frozen plasma administered to the HES 130/0.4 (274 518 mL) compared with the HES 200/0.5 group (251 385 mL). The trial of Neff et al. is the third randomized trial in brain injury to be prematurely discontinued because of serious complications in HES recipients. One of these was a multicenter trial of 88 acute ischemic stroke patients (9), in which there was significantly increased mortality related to cerebral edema in recipients of HES 200/0.5. In the other involving 70 patients with acute ischemic stroke (10), clinical deterioration occurred in 8 HES 200/0.5 recipients versus none of the control group patients (P 0.01). In the abstract of their paper Neff et al. conclude that “HES 130/0.4 can safely be used in critically ill head trauma patients over several days at doses of up to 70 mL · kg 1 · d . ” This sanguine assessment appears difficult to justify in light of the high incidence of intracranial bleeding complications in both study groups as well as the other similar effects of HES 130/0.4 compared with HES 200/0.5, a HES preparation consistently associated with increased risk of hemorrhagic and other serious complications in brain injury patients. Indeed, the preponderance of currently available evidence suggests that HES is not safe in brain injury indications.