Effect of hemodilution with diaspirin cross-linked hemoglobin on intracranial pressure, cerebral perfusion pressure, and fluid requirements after head injury and shock

Abstract

Hemodilution has been shown to increase cerebral blood flow (CBF) and reduce lesion volume in models of occlusive cerebral ischemia, but it has not been evaluated in the setting of head trauma and shock in which ischemia is thought to play a role in the evolution of secondary injury. In a porcine model of brain injury and shock the authors compared hemodilution with diaspirin cross-linked hemoglobin (DCLHb) to a standard resuscitation regimen using Ringer's lactate solution and shed blood. After creation of a cryogenic brain injury followed by hemorrhage, the animals received a bolus of either 4 ml/kg of Ringer's lactate solution (Group 1, six animals) or DCLHb (Group 2, six animals), followed by infusion of Ringer's lactate solution to restore mean arterial pressure (MAP) to baseline. Group 1 received shed blood 1 hour after hemorrhage (R1) in the form of packed red blood cells. Group 2 received shed blood only for an Hb count of less than 5 g/dl. The animals were monitored for 24 hours. At R1, Group 2 had a significantly greater cerebral perfusion pressure ([CPP] 88 +/- 5.7 vs. 68 +/- 2.4 mm Hg, p < 0.05). By 3 hours after hemorrhage (R3) Group 2 had a significantly lower Hb concentration (8.5 +/- 0.4 vs. 12.1 +/- 0.3 g/dl, p < 0.05) and a significantly lower intracranial pressure ([ICP] 9 +/- 0.8 vs. 14 +/- 0.6 mm Hg, p < 0.05). The total 24-hour fluid requirement was significantly less in Group 2 (10,654 +/- 505 ml vs. 15,542 +/- 1094 ml, p < 0.05) There was no difference between the groups regarding levels of regional CBF in the injured hemisphere. Cerebral O2 delivery was not significantly different between groups at any time. Lesion volume as determined at postmortem examination was not significantly different between the groups. The increased MAP and CPP and lower ICP observed in the Group 2 animals indicate that hemodilution with DCLHb may be beneficial in the treatment of head injury and shock.

Haemoglobin management in acute brain injury

“…Although current evidence supports a restrictive RBCT strategy (haemoglobin $7 g/dl) in general critical care patients without serious cardiac disease [2,3,4 & ,5 & ], the optimal haemoglobin (Hgb) and transfusion trigger for TBI, AIS or SAH patients has still to be fully elucidated and there is great variance in how these patients are transfused [6,7 & ] with convincing arguments for both a liberal (Hgb $10 g/dl) and restrictive RBCT strategy [8 & -10 & ]. As anaemia induces cerebral vasodilatation, this may exacerbate cerebral oedema and increase intracranial pressure (ICP; [23]). This correction of hypoxia or metabolism rather than anaemia may be more important when considering outcome [13 && ,14 && ].…”

Effect of haemodilution with diaspirin cross‐linked haemoglobin on the oxygen reserve in a rodent model of surgical blood loss

“…The authors concluded that the presence of the HBOC did not improve systemic DO 2 in comparison to the control haemodiluent (HES). Other investigators have also reported decreases in cardiac output in response to DCLHb (Chappell et al ., 1997), and other HBOCs, including those derived from bovine haemoglobin (Kasper et al ., 1998) and human haemoglobin. (Biro et al ., 1991; Migita et al ., 1997; Winslow et al ., 1998) reported a decrease in cardiac output when using a dextran–stroma‐free human haemoglobin solution as a haemodiluent.…”

Resuscitation From Hemorrhagic Shock With Hboc-201 in the Setting of Traumatic Brain Injury

“…Another study using DCLHb in a small animal model of brain injury without associated hemorrhagic shock showed that DCLHb, given in equivalent volumes as other agents, increased CPP, decreased ICP, and increased CBF (29). In addition, the previously mentioned large animal models using DCLHb used equivalent volumes of agent or LR in the initial resuscitation and showed improved CPP (22,30,31). Therefore, evaluating this study in the context of previously published work with other HBOCs, we believe that the decrease in CBF after resuscitation is most likely secondary to the significantly reduced amount of resuscitation fluid required by the HBOC group.…”