Fentanyl vs. Morphine in Head Injury
Abstract & Commentary
Synopsis: Boluses of fentanyl or morphine increased intracranial pressure equally in patients with elevated ICP and decreased cerebral perfusion pressure. Cerebral blood flow was unchanged as determined by transcranial doppler and jugular venous oxygen saturation, and there was no difference in response between patients with impaired or intact autoregulation.
Source: de Nadal M, et al. Anesthesiology 2000; 92(1): 11-19.
To evaluate the effects of narcotics on cerebral hemodynamics and intracranial pressure (ICP) in head-injured patients, de Nadal and colleagues compared the effects of boluses of morphine (0.2 mg/kg) and fentanyl (2 mcg/kg) in 29 patients being treated for severe head injury. Each drug was used in each patient, separated by 24 hours, and the order of administration was assigned randomly. Patients were paralyzed with vecuronium, sedated with midazolam, and provided non-narcotic analgesia. All patients were maintained at normothermia, with a normal arterial blood acid base balance, a hemoglobin level above 10 g/mL, and a central venous pressure (CVP) of around 10 mm Hg. Cerebral perfusion pressure (CPP) was maintained above 60 mm Hg with a phenylepherine drip if needed and ICP was kept below 20 mm Hg with intravenous boluses of mannitol plus hyperventilation if needed. Change in cerebral blood flow was estimated by transcranial doppler (TCD) of the middle cerebral artery (MCA) and also by the difference in arterial oxygen saturation and JVSO2. Autoregulation to CO2 was determined prior to each narcotic administration by altering the ventilator to produce a change in CO2 and calculating the percentage change in cerebral blood flow (CBF) that resulted.
All patients had intact autoregulation to CO2, having at least a 1% change in CBF for each mm Hg change in CO2. Autoregulation to blood pressure was determined using a phenylepherine infusion to raise arterial blood pressure by 25%. Patients demonstrating more than a 20% increase in CBF or a rise in ICP were considered to have impaired autoregulation to blood pressure.
Thirty patients were entered into the study and were studied within three days of injury. They averaged 30 years of age and had a Glasgow Coma Scale score between 3 and 8. Two patients became unstable during the protocol and were excluded from the analysis. There were 29 studies completed with each drug. Narcotics were studied blindly with cerebral hemodynamics determined frequently over a one-hour period following injection. Forty percent to 60% of patients had impaired systemic blood pressure autoregulation during one of the study periods.
On the average, systemic blood pressure and CPP fell and ICP rose significantly in the first five minutes following administration of either drug. At 60 minutes, blood pressure and CPP remained reduced but ICP had returned to baseline or had fallen slightly below baseline. There was no difference between the two drugs in the group as a whole. However, in patients with intact blood pressure autoregulation, after the initial significant rise, ICP fell further and more promptly in the hour following morphine than was observed in those patients with impaired autoregulation, despite similar systemic hemodynamics. Due to the small number of patients and the wide standard deviation in ICP values, this difference did not reach statistical significance. There was no difference in the response to fentanyl and ICP remained above baseline in both subgroups.
Venous saturation and CBF remained unchanged in all groups at all times. TCD indicated no change in blood flow velocity in the middle cerebral artery. No change in CBF was detected following either drug, at any time, in patients with or without intact autoregulation to blood pressure.
COMMENT BY CHARLES G. DURBIN, Jr., MD, FCCM
This study suggests that either morphine or fentanyl may be used safely in patients with severe head injury. Both drugs produced an initial rise in ICP and a fall in CPP but preserved global CBF, even in patients with impaired autoregulation. If only ICP and systemic blood pressure are being monitored, fear of a fall in CBF due to decreased CPP may stimulate the clinician to augment blood pressure or treat the rise in ICP. These responses appear unnecessary and may be harmful, especially if hyperventilation is used.
This study demonstrates two important facts. All of the patients included in this study had intact responses to CO2, despite a severe degree of brain injury—the outcome was death in 27%, or severe disability in nearly half of the patients studied. CBF was preserved in all patients, and there was no cerebral hemodynamic difference associated with changes in CPP and ICP in those with and without preserved autoregulation.
While it appears that there were no changes in CBF associated with narcotic-induced changes in CPP, blood pressure, and ICP, limitations of the methods must be borne in mind. When jugular venous oxygen saturation is used to estimate changes in CBF, only the global and not regional changes are identified. TCD may be useful in detecting regional changes, but the sensitivity of this technique is relatively poor. Only small changes in variables (3-4 mm Hg) occurred during the experiment and extrapolation that larger changes can be safely tolerated is unwarranted.
From this study, it is not clear what is responsible for the rise in ICP following narcotic administration in head-injured patients. Autoregulatory vasodilatation is an unlikely mechanism in these patients since there was no difference between those with intact vs. impaired autoregulation of cerebral perfusion. Possibly a direct vascular action of opioids or an indirect action through neurotransmitter release is responsible. More study is needed to elucidate the responsible mechanisms.
Cerebral blood flow in patients with severe head injury:
a. is reduced by fentanyl but not by morphine used for sedation.
b. is reduced by morphine but not by fentanyl used for sedation.
c. is reduced by both morphine and fentanyl.
d. is unaltered by either morphine or fentanyl.
e. is reduced by opioids in patients with impaired autoregulation.
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