The effects of perfluorocarbon dosing strategy on cerebral blood flow when starting partial liquid ventilation: A randomized, controlled, experimental study


Introduction: Partial liquid ventilation may benefit the lung disease in preterm neonates but intratracheal instillation of perfluorocarbon increases cerebral blood flow and may cause brain injury. We aimed to determine if the effects of perfluorocarbon administration on cerebral blood flow vary by dose-volume, rate of administration, endotracheal tube portal of entry, or closely targeting PaCO2. Methods: Forty-two dosing events (in eleven rabbits) were randomised to different dosing strategies, including a sham (i.e., placebo/control) dose of air over 20 min, 20 mL/kg of perfluorocarbon slowly over 20 min, 10 mL/kg of perfluorocarbon slowly over 20 min, 10 mL/kg of perfluorocarbon moderately fast over 10 min, 10 mL/kg of perfluorocarbon rapidly over 5 min, 10 mL/kg of perfluorocarbon slowly over 20 min via the endotracheal tube tip lumen (as opposed to the proximal end of the tube used in all other groups), or 10 mL/kg of perfluorocarbon slowly over 20 min whilst targeting a PaCO2 of 45 - 50 mmHg. Blood gases, haemodynamics, cortical cerebral blood flow and carotid flow were recorded continuously for 30 minutes from the start of each dose. Results: Carotid flow increased with 20 mL/kg perfluorocarbon and cortical cerebral blood flow was significantly more variable. Carotid and cortical cerebral blood flow increased using 10 mL/kg or 20 mL/kg with no difference between the two dose-volumes. There was no difference in cerebral blood flow by rate of administration, but carotid blood flow was more variable during slow administration. There were no differences in the increase in cerebral blood flow by portal of entry. If PaCO2 was maintained between 45 - 50 mmHg there was no increase in cerebral blood flow and there was less variable carotid flow. Conclusions: Cerebral blood flow increases with perfluorocarbon dosing. This occurs regardless of the dose-volume of perfluorocarbon. These effects were mitigated by closely targeting PaCO2.

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W. Davies, M. , R. Dunster, K. , F. Fraser, J. and B. Colditz, P. (2012) The effects of perfluorocarbon dosing strategy on cerebral blood flow when starting partial liquid ventilation: A randomized, controlled, experimental study. Open Journal of Pediatrics, 2, 197-213. doi: 10.4236/ojped.2012.23033.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Costeloe, K., Hennessy, E., Gibson, A.T., Marlow, N. and Wilkinson, A.R. (2000) The EPICure study: Outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics, 106, 659-671. doi:10.1542/peds.106.4.659
[2] Hennessy, E.M., Bracewell, M.A., Wood, N., Wolke, D., Costeloe, K., Gibson, A. and Marlow, N. for the EPICure Study Group (2008) Respiratory health in pre-school and school age children following extremely preterm birth. Archives of Diseases in Childhood, 93, 1037-1043. doi:10.1136/adc.2008.140830
[3] Leach, C.L., Greenspan, J.S., Rubenstein, S.D., Shaffer, T.H., Wolfson, M.R., Jackson, J.C., DeLemos, R. and Fuhrman, B.P. for the LiquiVent Study Group (1996) Partial liquid ventilation with perflubron in premature infants with severe respiratory distress syndrome. The New England Journal of Medicine, 335, 761-767. doi:10.1056/NEJM199609123351101
[4] Blassnig, N., Dietl, S., Tschirch, E., Burkhardt, W., Wemh?ner, A. and Rüdiger, M. (2009) Intratracheal application of PFC diminishes the hyperoxia-mediated impairment of postnatal lung development. Acta Paediatrica, 98, 7.
[5] Vohr, B. and Ment, L.R. (1996) Intraventricular hemorrhage in the preterm infant. Early Human Development, 44, 1-16. doi:10.1016/0378-3782(95)01692-9
[6] Ballabh, P. (2010) Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatric Research, 67, 1-8. doi:10.1203/PDR.0b013e3181c1b176
[7] Perlman, J.M. (2009) The relationship between systemic hemodynamic perturbations and periventricular-intraventricular hemorrhage—A historical perspective. Seminars in Pediatric Neurology, 16, 191-199. doi:10.1016/j.spen.2009.09.006
[8] Davies, M.W., Dunster, K.R., Wilson, K. and Colditz, P.B. (2010) Perfluorocarbon dosing when starting partial liquid ventilation: Haemodynamics and cerebral blood flow in preterm lambs. Neonatology, 97, 144-153. doi:10.1159/000239768
[9] Davies, M.W., Dunster, K.R., Wilson, K. and Colditz, P.B. (2010) The effect of the dose volume of perfluorocarbon when starting partial liquid ventilation. Journal of Paediatrics and Child Health, 46, 714-722. doi:10.1111/j.1440-1754.2010.01828.x
[10] Dunster, K.R. and Davies, M.W. (2004) A novel mounting device to attach intracranial probes to the skull for use in experimental research models. Physiological Measurement, 25, N11-N14.doi:10.1088/0967-3334/25/2/N01
[11] Tutuncu, A.S., Faithfull, N.S. and Lachmann, B. (1993) Comparison of ventilatory support with intratracheal perfluorocarbon administration and conventional mechanical ventilation in animals with acute respiratory failure. American Journal of Respiratory and Critical Care Medicine, 148, 785-792. doi:10.1164/ajrccm/148.3.785
[12] Lim, C.M., Domino, K.B., Glenny, R.W. and Hlastala, M.P. (2001) Effect of increasing perfluorocarbon dose on VA/Q distribution during partial liquid ventilation in acute lung injury. Anesthesiology, 94, 637-642. doi:10.1097/00000542-200104000-00018
[13] Lim, C.-M., Yang, S.-H., Kang, J.-L. and Koh, Y. (2002) Effect of ventilation mode on gas exchange during partial liquid ventilation at different perfluorocarbon doses in surfactant-depleted lung. Lung, 179, 245-255. doi:10.1007/s004080000065
[14] Suh, G.Y., Chung, M.P., Park, S.J., Koh, Y., Kang, K.W., Kim, H., Han, J., Rhee, C.H. and Kwon, O.J. (2000) Partial liquid ventilation shows dose-dependent increase in oxygenation with PEEP and decreases lung injury associated with mechanical ventilation. Journal of Critical Care, 15, 103-112. doi:10.1053/jcrc.2000.16463
[15] Fessler, H.E. and Pearse, D. (2000) Accuracy of hemodynamic measurements during partial liquid ventilation with perflubron. American Journal of Respiratory and Critical Care Medicine, 162, 1372-1376.
[16] Davies, M.W. and Dunster, K.R. (2000) The effect of perfluorocarbon vapour on the measurement of respiretory tidal volume during partial liquid ventilation. Physiological Measurement, 21, N23-N30. doi:10.1088/0967-3334/21/3/402
[17] Takeuchi, T., Horiuchi, J. and Terada, N. (1989) Central vasomotor control of the rabbit portal vein. Pflügers Archiv European Journal of Physiology, 413, 348-353. doi:10.1007/BF00584482
[18] National Health and Medical Research Council (Australia) (2004) Australian code of practice for the care and use of animals for scientific purposes. 7th Edition, Australian Government Publishing Service, Canberra.
[19] Weiswasser, J., Lueders, M. and Stolar, C.J.H. (1998) Pressure-versus volume-cycled ventilation in liquid-ventilated neonatal piglet lungs. Journal of Pediatric Surgery, 33, 1158-1162. doi:10.1016/S0022-3468(98)90551-6
[20] Hummler, H.D., Schulze, A., Pohlandt, F. and Thome, U. (2000) Dynamics of breathing during partial liquid ventilation in spontaneously breathing rabbits supported by elastic and resistive unloading. Pediatric Research, 47, 392-397. doi:10.1203/00006450-200003000-00018
[21] Shashikant, M.P., Badellino, M.M., Cooper, B., Shaffer, T.H., Myers, S.I. and Wolfson, M.R. (2002) Physico-chemical properties of perfluorochemical liquids influence ventilatory requirements, pulmonary mechanics, and microvascular permeability during partial liquid ventilation following intestinal ischemia/reperfusion injury. Critical Care Medicine, 30, 2300-2305. doi:10.1097/00003246-200210000-00019
[22] Burkhardt, W., Proquitté, H., Krause, S., Wauer, R.R. and Rüdiger, M. (2004) Changes in FiO2 affect PaO2 with minor alterations in cerebral concentration of oxygenated hemoglobin during liquid ventilation in healthy piglets. Intensive Care Medicine, 30, 315-320. doi:10.1007/s00134-003-2090-7
[23] Hernan, L.J., Fuhrman, B.P., Papo, M.C., Steinhorn, D.M., Leach, C.L., Salman, N., Paczan, P.R. and Kahn, B. Cardiorespiratory effects of perfluorocarbon-associated gas exchange at reduced oxygen concentrations. Critical Care Medicine, 23, 553-559. doi:10.1097/00003246-199503000-00022
[24] Burkhardt, W., Proquitté, H., Krause, S., Wauer, R.R. and Rüdiger, M. (2002) Cerebral oxygenation is affected by filling mode and perfluorochemical volume in partial liquid ventilation of healthy piglets. Biology of the Neonate, 82, 250-256. doi:10.1159/000065886
[25] McLaughlin, G.E., Kulatunga, S., Kuluz, J.W., Gelman, B. and Schleien, C.L. (2001) Cerebral blood flow during partial liquid ventilation in surfactant deficient lungs under varying ventilation strategies. Pediatric Critical Care Medicine, 2, 88-92. doi:10.1097/00130478-200101000-00017
[26] Dimmitt, R.A., Beckman, S.A., Halamek, L.P., Moss, R.L., Mickas, N.A., Falco, D.A., Chubb, C. and Skarsgard, E.D. (2002) Effects of partial liquid ventilation on cerebral blood flow and cerebral metabolism in neonatal lambs. Journal of Pediatric Surgery, 37, 840-844. doi:10.1053/jpsu.2002.32884
[27] Wolfson, M.R. and Shaffer, T.H. (2005) Pulmonary applications of perfluorochemical liquids: Ventilation and beyond. Paediatric Respiratory Reviews, 6, 117-127. doi:10.1016/j.prrv.2005.03.010
[28] Greenough, A. (2006) High frequency oscillation and liquid ventilation. Paediatric Respiratory Reviews, 7, S186-S188. doi:10.1016/j.prrv.2006.04.207

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