correspondence
population, dose and duration of therapy, adherence to therapy, and immortal time bias are some of the many factors that contribute to difficulties in assessing the true effectiveness of a drug. We also agree that randomized, controlled trials remain the standard for the evaluation of drug efficacy and effectiveness.4 Gerard J. Criner, M.D. Temple University School of Medicine Philadelphia, PA [email protected]
John E. Connett, Ph.D. Helen Voelker, B.A.
Since publication of their article, the authors report no further potential conflict of interest. 1. Milara J, Mata M, Mauricio MD, Donet E, Morcillo EJ, Cor-
tijo J. Sphingosine-1-phosphate increases human alveolar epithelial IL-8 secretion, proliferation and neutrophil chemotaxis. Eur J Pharmacol 2009;609:132-9. 2. Derendorf H, Nave R, Drollmann A, Cerasoli F, Wurst W. Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma. Eur Respir J 2006;28:1042-50. 3. Singh SD, Whale C, Houghton N, Daley-Yates P, Kirby SM, Woodcock AA. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in chronic obstructive pulmonary disease. Br J Clin Pharmacol 2003;55:375-81. 4. Suissa S. Co-morbidity in COPD: the effects of cardiovascular drug therapies. Respiration 2010;80:3-7. DOI: 10.1056/NEJMc1408400
University of Minnesota Minneapolis, MN
Traumatic Intracranial Hypertension To the Editor: We think that Stocchetti and Maas, in their review article (May 29 issue),1 should have provided more information on the use of transcranial Doppler ultrasonography for noninvasive monitoring of intracranial pressure. With the use of this approach, the pulsatility index, which is dependent on distal vascular resistance, is strongly correlated with intracranialpressure values in various clinical conditions.2,3 This approach also allows evaluation of the autoregulation of cerebral blood flow, which cannot be evaluated by means of invasive devices.4 However, transcranial Doppler ultrasonography cannot replace invasive monitors of intracranial pressure, since it is not a continuous-monitoring device. Its best role might be as a screening tool to determine which patients have elevated intracranial pressure.5 Jean Cotte, M.D. Pierre Esnault, M.D. Bertrand Prunet, M.D. Saint Anne Military Teaching Hospital Toulon, France
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Stocchetti N, Maas AIR. Traumatic intracranial hyperten-
sion. N Engl J Med 2014;370:2121-30. 2. Wakerley BR, Kusuma Y, Yeo LL, et al. Usefulness of transcranial Doppler-derived cerebral hemodynamic parameters in
the noninvasive assessment of intracranial pressure. J Neuroimaging 2014 March 5 (Epub ahead of print). 3. Gura M, Elmaci I, Sari R, Coskun N. Correlation of pulsatility index with intracranial pressure in traumatic brain injury. Turk Neurosurg 2011;21:210-5. 4. Panerai RB. Transcranial Doppler for evaluation of cerebral autoregulation. Clin Auton Res 2009;19:197-211. 5. Tazarourte K, Atchabahian A, Tourtier JP, et al. Pre-hospital transcranial Doppler in severe traumatic brain injury: a pilot study. Acta Anaesthesiol Scand 2011;55:422-8. DOI: 10.1056/NEJMc1407775
To the Editor: Stocchetti and Maas highlight the factors that contribute to increased intracranial hypertension. However, their article overlooks head position as a major factor that affects intracranial hypertension in patients with traumatic brain injury. Patients with traumatic brain injury benefit from increased cerebral venous outflow, which results from elevation of the head and maintaining the head in a neutral position. Elevation by 15 to 30 degrees is also associated with a shift of the cerebrospinal fluid from the intracranial compartment to the spinal compartment. The consequent reduction in intracranial pressure, cerebral blood flow, or both after this elevation of the head is favorable in most patients.1,2 If this maneuver is performed during monitoring of systemic arterial and intracranial pressure, to maintain appropriate cerebral perfusion pressure,
n engl j med 371;10 nejm.org september 4, 2014
The New England Journal of Medicine Downloaded from nejm.org at MCGILL UNIVERSITY LIBRARY on December 9, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
971
The
n e w e ng l a n d j o u r na l
the transducers must be appropriately set to zero at the level of the foramen of Monro or (more practically) at the level of the external auditory meatus. Ata Mahmoodpoor, M.D. Samad E.J. Golzari, M.D. Tabriz University of Medical Sciences Tabriz, Iran
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Feldman Z, Kanter MJ, Robertson CS, et al. Effect of head
elevation on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in head-injured patients. J Neurosurg 1992;76:207-11. 2. Ng I, Lim J, Wong HB. Effects of head posture on cerebral hemodynamics: its influences on intracranial pressure, cerebral perfusion pressure, and cerebral oxygenation. Neurosurgery 2004;54:593-7. DOI: 10.1056/NEJMc1407775
of
m e dic i n e
our article and in our algorithm for the treatment of intracranial pressure (Fig. 2 of the article). However, we strongly suggest that cerebral perfusion pressure should be preserved when intracranial pressure is treated. Rosner and Coley4 warned that elevation of the head was associated with a risk of reducing intracranial pressure at the expense of an even greater reduction in cerebral perfusion pressure. In their series involving 18 patients, 4 had further increases in intracranial pressure after the decrease in perfusion pressure induced by elevation of the head. In the study by Feldman et al. that was cited by Mahmoodpoor and Golzari, 5 patients (23%) had reduced cerebral blood flow owing to elevation of the head, although no adverse effects on cerebral perfusion pressure and cerebral blood flow were reported when data were averaged for the whole group. It is our practice to check whether moderate elevation of the head (by 15 to 30 degrees) may contribute to control of intracranial pressure without dangerous reductions in cerebral perfusion pressure in individual patients. In many cases, as indicated by our colleagues, slight elevation of the head helps, but in some cases it does not. Perhaps this is a good example of individualized therapy, which we advocated in our criticism of “one size fits all” approaches.
The Authors Reply: Cotte and coworkers underscore the potential of transcranial Doppler ultrasonography for noninvasive assessment of intracranial pressure. The evidence supporting transcranial Doppler ultrasonography as an indicator of elevated intracranial pressure is extremely controversial. This method has been used to identify children who are at risk for elevated intracranial pressure, with unreliable re- Nino Stocchetti, M.D. sults.1 After initial enthusiasm about the use of Milan University this method in adults, worrisome results have Milan, Italy been reported, especially in patients with preAndrew I.R. Maas, M.D., Ph.D. existing vascular diseases.2 A comprehensive University Hospital 3 analysis by the Cambridge Group involving 290 Antwerp Edegem, Belgium patients with head injury concluded that “overall Since publication of their article, Dr. Stocchetti reports rethe value of transcranial Doppler ultrasonogra- ceiving an honorarium from Johnson & Johnson. No further phy to assess intracranial pressure noninvasively potential conflict of interest relevant to this letter was reported. is very limited.” As Cotte and coauthors admit, 1. Figaji AA, Zwane E, Fieggen AG, Siesjo P, Peter JC. Transcratranscranial Doppler ultrasonography cannot re- nial Doppler pulsatility index is not a reliable indicator of intracranial pressure in children with severe traumatic brain injury. place invasive monitoring of intracranial pres- Surg Neurol 2009;72:389-94. sure. In our opinion, its potential for screening 2. Ahmad M, Legrand M, Lukaszewicz AC, Charlier P, Mateo J, patients who are at risk for elevated intracranial Payen D. Transcranial Doppler monitoring may be misleading in prediction of elevated ICP in brain-injured patients. Intensive pressure remains insufficiently proved. Care Med 2013;39:1150-1. Mahmoodpoor and Golzari recommend ele- 3. Zweifel C, Czosnyka M, Carrera E, de Riva N, Pickard JD, vation of the head. We fully agree that venous Smielewski P. Reliability of the blood flow velocity pulsatility index for assessment of intracranial and cerebral perfusion presoutflow from the brain is extremely important sures in head-injured patients. Neurosurgery 2012;71:853-61. and that any cause of elevated venous pressure, 4. Rosner MJ, Coley IB. Cerebral perfusion pressure, intracraas in the case of neck torsion or compression, nial pressure, and head elevation. J Neurosurg 1986;65:636-41. should be avoided, as we proposed in Table 2 of DOI: 10.1056/NEJMc1407775
972
n engl j med 371;10 nejm.org september 4, 2014
The New England Journal of Medicine Downloaded from nejm.org at MCGILL UNIVERSITY LIBRARY on December 9, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
population, dose and duration of therapy, adherence to therapy, and immortal time bias are some of the many factors that contribute to difficulties in assessing the true effectiveness of a drug. We also agree that randomized, controlled trials remain the standard for the evaluation of drug efficacy and effectiveness.4 Gerard J. Criner, M.D. Temple University School of Medicine Philadelphia, PA [email protected]
John E. Connett, Ph.D. Helen Voelker, B.A.
Since publication of their article, the authors report no further potential conflict of interest. 1. Milara J, Mata M, Mauricio MD, Donet E, Morcillo EJ, Cor-
tijo J. Sphingosine-1-phosphate increases human alveolar epithelial IL-8 secretion, proliferation and neutrophil chemotaxis. Eur J Pharmacol 2009;609:132-9. 2. Derendorf H, Nave R, Drollmann A, Cerasoli F, Wurst W. Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma. Eur Respir J 2006;28:1042-50. 3. Singh SD, Whale C, Houghton N, Daley-Yates P, Kirby SM, Woodcock AA. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in chronic obstructive pulmonary disease. Br J Clin Pharmacol 2003;55:375-81. 4. Suissa S. Co-morbidity in COPD: the effects of cardiovascular drug therapies. Respiration 2010;80:3-7. DOI: 10.1056/NEJMc1408400
University of Minnesota Minneapolis, MN
Traumatic Intracranial Hypertension To the Editor: We think that Stocchetti and Maas, in their review article (May 29 issue),1 should have provided more information on the use of transcranial Doppler ultrasonography for noninvasive monitoring of intracranial pressure. With the use of this approach, the pulsatility index, which is dependent on distal vascular resistance, is strongly correlated with intracranialpressure values in various clinical conditions.2,3 This approach also allows evaluation of the autoregulation of cerebral blood flow, which cannot be evaluated by means of invasive devices.4 However, transcranial Doppler ultrasonography cannot replace invasive monitors of intracranial pressure, since it is not a continuous-monitoring device. Its best role might be as a screening tool to determine which patients have elevated intracranial pressure.5 Jean Cotte, M.D. Pierre Esnault, M.D. Bertrand Prunet, M.D. Saint Anne Military Teaching Hospital Toulon, France
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Stocchetti N, Maas AIR. Traumatic intracranial hyperten-
sion. N Engl J Med 2014;370:2121-30. 2. Wakerley BR, Kusuma Y, Yeo LL, et al. Usefulness of transcranial Doppler-derived cerebral hemodynamic parameters in
the noninvasive assessment of intracranial pressure. J Neuroimaging 2014 March 5 (Epub ahead of print). 3. Gura M, Elmaci I, Sari R, Coskun N. Correlation of pulsatility index with intracranial pressure in traumatic brain injury. Turk Neurosurg 2011;21:210-5. 4. Panerai RB. Transcranial Doppler for evaluation of cerebral autoregulation. Clin Auton Res 2009;19:197-211. 5. Tazarourte K, Atchabahian A, Tourtier JP, et al. Pre-hospital transcranial Doppler in severe traumatic brain injury: a pilot study. Acta Anaesthesiol Scand 2011;55:422-8. DOI: 10.1056/NEJMc1407775
To the Editor: Stocchetti and Maas highlight the factors that contribute to increased intracranial hypertension. However, their article overlooks head position as a major factor that affects intracranial hypertension in patients with traumatic brain injury. Patients with traumatic brain injury benefit from increased cerebral venous outflow, which results from elevation of the head and maintaining the head in a neutral position. Elevation by 15 to 30 degrees is also associated with a shift of the cerebrospinal fluid from the intracranial compartment to the spinal compartment. The consequent reduction in intracranial pressure, cerebral blood flow, or both after this elevation of the head is favorable in most patients.1,2 If this maneuver is performed during monitoring of systemic arterial and intracranial pressure, to maintain appropriate cerebral perfusion pressure,
n engl j med 371;10 nejm.org september 4, 2014
The New England Journal of Medicine Downloaded from nejm.org at MCGILL UNIVERSITY LIBRARY on December 9, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
971
The
n e w e ng l a n d j o u r na l
the transducers must be appropriately set to zero at the level of the foramen of Monro or (more practically) at the level of the external auditory meatus. Ata Mahmoodpoor, M.D. Samad E.J. Golzari, M.D. Tabriz University of Medical Sciences Tabriz, Iran
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Feldman Z, Kanter MJ, Robertson CS, et al. Effect of head
elevation on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in head-injured patients. J Neurosurg 1992;76:207-11. 2. Ng I, Lim J, Wong HB. Effects of head posture on cerebral hemodynamics: its influences on intracranial pressure, cerebral perfusion pressure, and cerebral oxygenation. Neurosurgery 2004;54:593-7. DOI: 10.1056/NEJMc1407775
of
m e dic i n e
our article and in our algorithm for the treatment of intracranial pressure (Fig. 2 of the article). However, we strongly suggest that cerebral perfusion pressure should be preserved when intracranial pressure is treated. Rosner and Coley4 warned that elevation of the head was associated with a risk of reducing intracranial pressure at the expense of an even greater reduction in cerebral perfusion pressure. In their series involving 18 patients, 4 had further increases in intracranial pressure after the decrease in perfusion pressure induced by elevation of the head. In the study by Feldman et al. that was cited by Mahmoodpoor and Golzari, 5 patients (23%) had reduced cerebral blood flow owing to elevation of the head, although no adverse effects on cerebral perfusion pressure and cerebral blood flow were reported when data were averaged for the whole group. It is our practice to check whether moderate elevation of the head (by 15 to 30 degrees) may contribute to control of intracranial pressure without dangerous reductions in cerebral perfusion pressure in individual patients. In many cases, as indicated by our colleagues, slight elevation of the head helps, but in some cases it does not. Perhaps this is a good example of individualized therapy, which we advocated in our criticism of “one size fits all” approaches.
The Authors Reply: Cotte and coworkers underscore the potential of transcranial Doppler ultrasonography for noninvasive assessment of intracranial pressure. The evidence supporting transcranial Doppler ultrasonography as an indicator of elevated intracranial pressure is extremely controversial. This method has been used to identify children who are at risk for elevated intracranial pressure, with unreliable re- Nino Stocchetti, M.D. sults.1 After initial enthusiasm about the use of Milan University this method in adults, worrisome results have Milan, Italy been reported, especially in patients with preAndrew I.R. Maas, M.D., Ph.D. existing vascular diseases.2 A comprehensive University Hospital 3 analysis by the Cambridge Group involving 290 Antwerp Edegem, Belgium patients with head injury concluded that “overall Since publication of their article, Dr. Stocchetti reports rethe value of transcranial Doppler ultrasonogra- ceiving an honorarium from Johnson & Johnson. No further phy to assess intracranial pressure noninvasively potential conflict of interest relevant to this letter was reported. is very limited.” As Cotte and coauthors admit, 1. Figaji AA, Zwane E, Fieggen AG, Siesjo P, Peter JC. Transcratranscranial Doppler ultrasonography cannot re- nial Doppler pulsatility index is not a reliable indicator of intracranial pressure in children with severe traumatic brain injury. place invasive monitoring of intracranial pres- Surg Neurol 2009;72:389-94. sure. In our opinion, its potential for screening 2. Ahmad M, Legrand M, Lukaszewicz AC, Charlier P, Mateo J, patients who are at risk for elevated intracranial Payen D. Transcranial Doppler monitoring may be misleading in prediction of elevated ICP in brain-injured patients. Intensive pressure remains insufficiently proved. Care Med 2013;39:1150-1. Mahmoodpoor and Golzari recommend ele- 3. Zweifel C, Czosnyka M, Carrera E, de Riva N, Pickard JD, vation of the head. We fully agree that venous Smielewski P. Reliability of the blood flow velocity pulsatility index for assessment of intracranial and cerebral perfusion presoutflow from the brain is extremely important sures in head-injured patients. Neurosurgery 2012;71:853-61. and that any cause of elevated venous pressure, 4. Rosner MJ, Coley IB. Cerebral perfusion pressure, intracraas in the case of neck torsion or compression, nial pressure, and head elevation. J Neurosurg 1986;65:636-41. should be avoided, as we proposed in Table 2 of DOI: 10.1056/NEJMc1407775
972
n engl j med 371;10 nejm.org september 4, 2014
The New England Journal of Medicine Downloaded from nejm.org at MCGILL UNIVERSITY LIBRARY on December 9, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
