Neurology -- Correspondence for Chang and Lowenstein, 60 (1) 10-16

Correspondence published:

Reply to Latronico: Bernard S. Chang, Daniel H. Lowenstein, MD (28 April 2003)

Antiepileptic drug prophylaxis in severe traumatic brain injury: Nicola Latronico, Elena Cagnazzi (28 April 2003)

Reply to Latronico 28 April 2003

Bernard S. Chang,
Dept. of Neurology
Harvard,
Daniel H. Lowenstein, MD
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Re: Reply to Latronico

bchang{at}caregroup.harvard.edu Bernard S. Chang, et al.

Drs. Latronico and Cagnazzi raise a number of methodological issues regarding our practice parameter concerning antiepileptic drug prophylaxis in severe traumatic brain injury. [1]
We agree that it is ideal for clinical studies to report in detail their treatment assignment and outcome assessment techniques, including specific descriptions of how randomization was performed and how masked assessment (blinding) was maintained. In this way readers are assured of the rigor with which these processes were carried out. However, such standards of reporting [2] were not necessarily in place when many of our analyzed studies were published. We considered a study to be “randomized” if the publication clearly stated that treatments were assigned in a random manner, in accordance with the American Academy of Neurology’s classification-of-evidence scheme reproduced in Appendix 1 of our paper.
With regard to the concurrent use of sedative agents, this is one of many variables that may differ between a particular head-injured patient and the subjects enrolled in the studies we analyzed. As we mention in the paper, other factors (such as EEG results) may also influence the clinical decision on seizure prophylaxis. We encourage clinicians to make an informed decision appropriate for each patient, and to use our practice recommendations as adjuncts in decision-making to the extent that a patient’s situation is comparable to those encountered in our analyzed studies.
The reported rates of post-traumatic seizures, both early and late, certainly vary to some degree. Published epidemiological evidence from “modern-era” studies of closed and penetrating head injuries is needed to confirm the observations of the letter writers and others.
Finally, Drs. Latronico and Cagnazzi raise the issue of the definition of “severe” brain injury. As noted in our Methods, we searched the literature for studies of post-traumatic seizure prophylaxis following head injury of any severity, but all resulting appropriate studies enrolled only subjects who met their authors’ criteria for “severe” head injury and who were thus felt to be at high risk for seizures. Some variability exists in these criteria, but we feel that the study populations are broadly comparable. Although classifications based strictly on Glasgow Coma Scale scores are used by many, this is by no means universal and in fact, definitions incorporating other clinical or radiological findings are likely to be more useful. [3]
1. Chang BS, Lowenstein DH. Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury. Neurology 2003;60:10-16.
2. Begg C, Cho M, Eastwood S, et al. Improving the Quality of Reporting of Randomized Controlled Trials: The CONSORT Statement. JAMA 1996;276:637-639.
3. Masson F, Thicoipe M, Aye P, et al. Epidemiology of severe brain injuries: a prospective population-based study. J Trauma 2001;51:481-489.

Antiepileptic drug prophylaxis in severe traumatic brain injury 28 April 2003

Nicola Latronico,
Associate Professor
University of Brescia, Italy,
Elena Cagnazzi
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Re: Antiepileptic drug prophylaxis in severe traumatic brain injury

latronic{at}med.unibs.it Nicola Latronico, et al.

Chang and Lowenstein [1]conclude that phenytoin should be started as soon as possible after brain trauma (BT) to decrease the risk of early posttraumatic seizures (EPTS). We think that this conclusion is based on their incorrect scoring of selected studies. Furthermore, their conclusion does not consider the current use of sedative agents in patients with severe BT.
The authors classified the studies by Young et al [2], and Temkin et al [3] as class I studies. However, neither specify the randomization method. Proper randomization is crucial in high- quality trials, since it balances the groups for prognostic factors, known or unknown, provided large samples are used [4]. Furthermore, physicians responsible for entering the patients into the study are unaware of which treatment the next patient will receive, thus eliminating selection bias. Inappropriate or unclear randomization may yield inflated treatment effects [4]. Experts suggest a “guilty until proven” approach in cases where randomization is not adequately presented [4], and therefore neither studies can be considered as Level I evidence.
Sedation with benzodiazepines or propofol in association with potent analgesics is an integral part of the current medical treatment of severe BT patients. These drugs have antiepileptic properties and the frequency of seizures under these conditions is unknown. A recent study suggests a frequency of 3.6% [5], however concomitant sedative agents were not specified. After caring for hundreds of severe BT patients, we have never seen EPTS. All the studies considered by Chang and Lowenstein were performed at least 10 years ago and none specify concomitant sedative agents. The diagnosis of seizures was made clinically, indicating that patients were little or not sedated, and were not paralyzed.
Furthermore, although the review is supposed to be focused on severe BT, a large proportion of patients did not have a severe BT according to current definition (GCS < 8, patients not obeying, not speaking, not opening the eyes). In fact, in the Temkin study 60% of the patients had a GCS < 10, and in the Young study only 50% had a GCS<8. The recommendation to use prophylactic phenytoin to reduce the frequency of EPTS is based on weak evidence, and should not be implemented.
1.Chang BS, Lowenstein DH. Practice Parameter: Antiepileptic drug prophylaxis in severe traumatic brain injury. Report of the quality standards subcommittee of the american academy of neurology. Neurology 2003; 60:10-16
2.Young B, Rapp RP, Norton JA, Haack D, Tibbs PA, Bean JR. Failure of prophylactically administred phenytoin to prevent early posttraumatic seizures. J Neurosurg 1983; 58:231-235
3.Temkin NR, Dimken SS, Wilensky AJ, Keihm J, Chabal S., Winn HR. A randomised, double-blind study of phenytoin for the prevention of post- traumatic seizures. N Engl J Med 1990; 323:497-502
4.Latronico N, Botteri M, Minelli C, Zanotti C, Bertolini G, Candiani A. Quality of reporting of randomised controlled trials in the intensive care literature. A systematic analysis of paper published in Intensive Care Medicine over 26 years. Intensive Care Med 2002; 28: 1316-1323
5.Lee ST, Lui TN, Wong CW, et al. Early Seizures after Severe Closed Head Injury. Can J Neurol Sci 1997; 24:40-43