Neurology -- Correspondence for Koenig et al., 0 (2008) 10000304

Correspondence published:

Reversal of transtentorial herniation with hypertonic saline: Alexander Y. Zubkov, MD, PhD, Eelco F.M. Wijdicks (9 April 2008)

Reply from the authors: Robert D. Stevens, Matthew A. Koenig (9 April 2008)

Reversal of transtentorial herniation with hypertonic saline 9 April 2008

Alexander Y. Zubkov, MD, PhD,
Mayo Clinic
200 First Street SW, Rochester, MN,
Eelco F.M. Wijdicks
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Re: Reversal of transtentorial herniation with hypertonic saline

wijde{at}mayo.edu Alexander Y. Zubkov, MD, PhD, et al.

Over the years, The Hopkins' Neurocritical care group has carefully studied the effect of hypertonic solutions clinically and experimentally.
The recent report by Koenig et al invites the following comments. [1] Hypertonic saline or mannitol could improve neurological examination in a patient with a new mass. We and others have observed rapid dramatic changes with osmotic agents. For example, we have observed dilated pupils and extensor responses at baseline, but soon after injection, pupils normalize and improvement to localization to noxious stimuli is seen. Koenig and the editorialists suggest the immediacy of such a response is reversal of transtentorial herniation, but evidence of that is not provided; there are few clinical details except a GCS sum score and no CT or MR studies. We are not certain that the clinical improvement is due to decompression or dislodging of tissue squeezed through the tentorium. In fact, when the effects are studied in mannitol, change in midline shift is not observed as changes are too minimal or almost too subtle to catch the eye on serial MRI. [2] Many consider that osmotic diuresis cannot physiologically explain the rapid improvement (within 30 minutes or less in many patients). Alternatively, sudden hypertonicity may cause vasodilatation of the cerebral resistance vessels and with an intact autoregulation result in vasoconstriction, reduced cerebral volume, and decrease in intracranial pressure. Even that explanation�albeit plausible�may be based on some assumptions including increased intracranial pressure and intact autoregulation.
Perhaps a simpler explanation is a suddenly improved blood flow and oxygenation to the displaced ischemic upper brainstem. [3,4] Cerebral perfusion improved substantially within 30 minutes in subarachnoid hemorrhage in a recent study followed by later reduction of ICP, although admittedly a larger saline bolus was used in that study. [5]
Koenig et al excluded 62 patients with no serial neurological examination available for review who were treated with hypertonic saline. It would be interesting to know their outcome, and if poor, could in some way further diminish their claim that hypertonic saline results in successful reversal in a high proportion of patients. Documentation in these cases may have been less detailed because patients did not initially do well in the first place.
Finally we would like to point out that hypertonic saline�typically injected with a 30 cc syringe�requires a central venous access catheter because severe thrombophlebitis occurs with peripheral infusion. This could delay emergent management and its placement has the potential for complications such as pneumothorax. This is an issue when such an intervention is considered in patients in Stroke Units,in the Emergency Department or even in those en route to the hospital.
References
1. Koenig MA, Bryan M, Lewin JL 3rd, et al. Reversal of transtentorial herniation with hypertonic saline. Neurology 2008;70:1023-1029.
2. Videen TO, Zazulia AR, Manno EM. Mannitol bolus preferentially shrinks non infarcted brain in patients with ischemic stroke Neurology 2001:57:2120-2122.
3. Ritter A, Muizelaar J, Barnes T, et al. Brain Stem Blood Flow, Pupillary Response, and Outcome in Patients with Severe Head Injuries. Neurosurgery 1999;44:941-948.
4. Wijdicks EFM. Acute Brainstem Displacement without Uncal Herniation and Posterior Cerebral Artery Injury, Journal of Neurosurg,Neurol and Psychiatry 2008 in press.
5. Tseng MY,Al-Rawi PG,Czosnyka M, et al. Enhancement of cerebral blood flow using systemic hypertonic saline therapy improves outcome with poor-grade spontaneous subarachnoid hemorrhage. J Neurosurg 2007:274-284.
Disclosure: The authors report no disclosures.

Reply from the authors 9 April 2008

Robert D. Stevens,
Johns Hopkins University School of Medicine
Meyer 8-140, 600 N Wolfe St, Baltimore, MD 21209,
Matthew A. Koenig
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Re: Reply from the authors

rstevens{at}jhmi.edu Robert D. Stevens, et al.

We appreciate the observations of Drs. Wijdicks and Zubkov. Transtentorial herniation (TTH) refers both to a clinical syndrome and an anatomic entity. Radiographic evidence of TTH may be observed in the absence of clinical signs and vice versa. [6,7]
We evaluated patients with a clinical diagnosis of TTH, defined as the sudden onset of a dilated, unresponsive pupil and decline in consciousness which are widely accepted criteria. [8,9] While we found that 23.4% saline was associated with reversal of clinical evidence of TTH, our data do not elucidate the mechanisms underlying these changes. Given the diverse effects of hypertonic saline on intracranial physiology, it is possible that factors other than mechanical decompression contributed to the observed effects. We measured displacement of midline structures on CT scans obtained before and after TTH. However, we did not include these data because few scans were performed in the interval after herniation was recognized but before administration of 23.4% saline.
In order to evaluate the effect of 23.4% saline on TTH, we selected patients who met strict clinical criteria and who had adequate documentation of the neurological exam before and after administration. We excluded 62 patients with documentation that was insufficient to determine whether or not TTH occurred or was reversed. Our colleagues suggest that documentation in the excluded patients might have been inadequate because these patients were refractory to treatment, thus introducing a selection bias. To address this concern, we re-analyzed our data to determine the outcomes of the 62 excluded patients. If the excluded patients were treatment failures, one would expect a higher mortality rate than in the analyzed group. However, the in-hospital mortality for the excluded patients was 60% (37/62), which was slightly lower than the population included in the study (68%), arguing against therapeutic failure in the patients with incomplete documentation.
Brain herniation is a medical emergency analogous to cardiopulmonary arrest and delaying treatment in order to obtain central venous access is unacceptable. Thus 23.4% may only be used as a first-line hyperosmolar agent in patients with a pre-existing central venous catheter. In others, a peripherally compatible hyperosmolar agent such as mannitol should be given initially, until central access has been established. In our Neurosciences Critical Care Unit this has rarely been an issue, since a high proportion of patients who experience herniation already have central venous access.
References
6. Reich JB, Sierra J, Camp W, Zanzonico P, Deck MD, Plum F. Magnetic resonance imaging measurements and clinical changes accompanying transtentorial and foramen magnum brain herniation. Ann Neurol 1993;33:159-170.
7. Ropper AH. Lateral displacement of the brain and level of consciousness in patients with an acute hemispheral mass.N Engl J Med. 1986;314:953-958.
8. Meyer A. Herniation of the brain. Arch Neurol Psychiatry 1920;4:387-400.
9. Posner JB, Plum F. Plum and Posner's diagnosis of stupor and coma. 4th ed. New York: Oxford University Press; 2007.
Disclosure: The authors report no disclosures.