Skip to main content
SpringerLink
Log in

CO2 and indomethacin vasoreactivity in patients with head injury

  • Clinical Articles
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Summary

The purpose of this study was to compare the effect of hyper-ventilation and indomethacin on cerebral circulation, metabolism and pressures in patients with acute severe head injury in order to see if indomethacin may act supplementary to hyperventilation. Fourteen severely head injured patients entered the study. Intracranial pressure (ICP), mean arterial blood pressure (MABP) and cerebral perfusion pressure (CPP) were monitored continuously. Within the first four days after the trauma the CO2 and indomethacin vasoreactivities were studied by measurements of cerebral blood flow (CBF) (Cerebrograph 10a, intravenous133Xe technique) and arterio-venous difference of oxygen (AVdO2). Ischaemia was evaluated from changes in CBF, saturation of oxygen in the jugular bulb (SvjO2), lactate and lactate/oxygen index (LOI). Data are presented as medians and ranges, results are significant unless otherwise indicated.

Before intervention ICP was well controlled (14.8 (9–24) mmHg) and basic CBF level was 39.1 (21.6–75.0) ml/100 g/min). The arterio-venous oxygen differences were generally decreased (AVdO2 = 4.3 (1.8–8.1) ml/100 ml) indicating moderate luxury perfusion. Levels of CMRO2 were decreased (1.54 (0.7–3.2) ml/100 g/min) as well.

Duringhyperventilation (ΔAPaCO2 = 0.88 (0.62–1.55) kPa) CBF decreased with 11.8 (−33.4−29.7) %/kPa and ICP decreased with 3.8 (0–10) mmHg. AVdO2 increased 34.0 (4.0–139.2) %/kPa, MABP was unchanged, CMRO2 and CPP increased (ΔCPP = 3.9 (−10−20) mmHg). AVD (lactate) and LOI were unchanged. No correlations between CBF responses to hypocapnia and outcomes were observed.

An i.v. bolus dose ofindomethacin (30 mg) decreased CBF 14.7 (−16.7−57.4) % and ICP decreased 4.3 (−1−17) mmHg. AVdO2 increased 27.8 (−40.0−66.7)%, MABP (ΔMABP = 4.9 (−2−21) mmHg) and CPP (ΔCPP = 8.7 (3–29) mmHg) increased while CMRO2 was unchanged. No changes in AVd (lactate) and LOI indicating cerebral ischaemia were found.

Compared to hyperventilation (changes per 1 kPa, at PaCO2 level = 4.05 kPa) the changes in MABP, CPP and CBF were significantly greater after indomethacin, while the changes in AVdO2, ICP, SvjO2, and LOI were of the same order of magnitude.

Nocorrelation between relative reactivities to indomethacin and CO2, evaluated from changes in CBF and AVdO2, or between the decrease in ICP after the two procedures were found. Thus, some patients reacted to indomethacin but not to hyperventilation, and vice versa.

These results suggest that indomethacin and hyperventilation might act independently, or in a complementary fashion in the treatment of patients with severe head injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Armstead WM, Mirro R, Busija DW, Leffler CW (1991) Opioids and the prostanoid system in the control of cerebral blood flow in hypotensive piglets. J Cereb Blood Flow Metab 11: 380–387

    PubMed  Google Scholar 

  2. Armstead WM, Mirro R, Busija DW, Leffler CW (1990) Prostanoids modulate opioid cerebrovascular responses in newborn pigs. J Pharm Exp Ther 255: 1083–1089

    Google Scholar 

  3. Dahlgren N, Nilsson B, Sakabe T, Siesjö BK (1981) The effect of indomethacin on cerebral blood flow and oxygen consumption in the rat at normal and increased carbon dioxide tensions. Acta Physiol Scand 111: 475–485

    PubMed  Google Scholar 

  4. DeGiuilo PA, Roth RA, Mishra OP, Delivoria-Papadopolos W, Wagerle LC (1989) Effect of indomethacin on the regulation of cerebral blood flow during respiratory alkalosis in newborn piglets. Pediatr Res 26: 593–597

    PubMed  Google Scholar 

  5. Edwards AD, Wyatt JS, Richardson C, Potter A, Cope M, Delpy DT, Reynolds EOR (1990) Effects of indomethacin on cerebral haemodynamics in very preterm infants. Lancet 335: 1491–1495

    PubMed  Google Scholar 

  6. Edvinsson L, MacKenzie ET, McCulloch J (1993) Cerebral blood flow and metabolism. Raven, New York, pp 354–362

    Google Scholar 

  7. Ellis EF, Police RJ, Yancey L, McKinney JS, Amruthesh SC (1990) Dilatation of cerebral arterioles by cytocrome P-450 metabolites of arachidonic acid. Am J Physiol 259 (Heart Circ Physiol 28): H1171-H1177

    PubMed  Google Scholar 

  8. Jensen K, Öhrström J, Cold GE, Astrup J (1991) The effects of indomethacin on intracranial pressure, cerebral blood flow and cerebral metabolism in patients with severe head injury and intracranial hypertension. Acta Neurochir (Wien) 108: 116–121

    Google Scholar 

  9. Messeter K, Nordström C-H, Sundbärg G, Algotsson L, Ryding E (1986) Cerebral hemodynamics in patients with acute severe head trauma. J Neurosurg 64: 231–237

    PubMed  Google Scholar 

  10. Miller JD, Becker DP, Ward JD, Sullivan HG, Adams WE, Rosner MJ (1977) Significance of intracranial hypertension in severe head injury. J Neurosurg 47: 503–516

    PubMed  Google Scholar 

  11. Miller JD (1981) Barbiturates and raised intracranial pressure. Ann Neurol 6: 189–193

    Google Scholar 

  12. Moskopp D, Ries F, Wassmann H, Nadstawek J (1991) Barbiturates in severe head injuries? Neurosurg Rev 14: 195–202

    PubMed  Google Scholar 

  13. Muizelaar JP, Marmarou A, Ward JD, Kontos HA, Choi SC, Becker DP, Gruemer H, Young HF (1991) Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg 75: 731–739

    PubMed  Google Scholar 

  14. Pickard JD, MacKenzie ET (1973) Inhibition of prostaglandin synthesis and the response of baboon cerebral circulation to carbon dioxide. Nature New Biol 245: 187–188

    PubMed  Google Scholar 

  15. Robertson CS, Narayan RK, Gokaslan ZL, Pahwa R, Grossman RG, Caram P, Allen E (1989) Cerebral arteriovenous oxygen difference as an estimate of cerebral blood flow in comatose patients. J Neurosurg 70: 222–230

    PubMed  Google Scholar 

  16. Sakabe T, Siesjö BK (1979) The effect of indomethacin on blood flow metabolism couple in the brain under normal, hypercapnic and hypoxic conditions. Acta Physiol Scand 107: 283–284

    PubMed  Google Scholar 

  17. Schalèn W, Messeter K, Nordström CH (1991) Cerebral vasoreactivity and the prediction of outcome in severe traumatic brain lesions. Acta Anaesthesiol Scand 35: 113–122

    PubMed  Google Scholar 

  18. Wang Q, Paulson OB, Lassen NA (1993) Indomethacin abolishes cerebral blood flow increase in response to acetazolamide-induced extracellular acidosis: a mechanism for its effect on hypercapnia. J Cereb Blood Flow Metab 13: 724–727

    PubMed  Google Scholar 

  19. Ward JD, Becker DP, Choi SC, Marmarou A, Wood C, Newlon PG, Keenan R (1985) Failure of prophylactic barbiturate coma in the treatment of severe head injury. J Neurosurg 62: 383–388

    PubMed  Google Scholar 

  20. Wennmalm Å, Carlsson I, Edlund A, Eriksson S, Kaijser L, Nowak S (1984) Central and peripheral haemodynamic effects of non-steroidal antiinflammatory drugs in man. Arch Neurol [Suppl 7]: 351–359

    Google Scholar 

  21. Wennmalm Å, Eriksson S, Wahren J (1981) Effect of indomethacin on basal and carbon dioxide stimulated cerebral blood flow in man. Clin Physiol 1: 227–234

    Google Scholar 

  22. Öhrström J, Jensen K, Nissen I, Bünemann L, Haase J (1989) Effect of indomethacin on cerebral blood flow at hypo-, nor-mo- and hypercapnia in man. Scand Neurosurg Soc Umeå, Sweden, Abstract 25

    Google Scholar 

  23. Pickard JD, MacKenzie ET (1973) Inhibition of prostaglandin synthesis and the response of baboon cerebral circulation to carbon dioxide. Nature New Biol 245: 187–188

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroanaesthesia, Århus University Hospital, Århus, Denmark

    B. Dahl, G. E. Cold & K. Jensen

  2. Department of Neurosurgery, Århus University Hospital, Århus, Denmark

    B. Bergholt, J. Astrup, B. Mosdal & J. O. Kjærsgaard

Authors
  1. B. Dahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Bergholt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. E. Cold
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Astrup
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. Mosdal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. O. Kjærsgaard
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dahl, B., Bergholt, B., Cold, G.E. et al. CO2 and indomethacin vasoreactivity in patients with head injury. Acta neurochir 138, 265–273 (1996). https://doi.org/10.1007/BF01411736

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01411736

Keywords

Search

Navigation