Original Contribution

Impact of positive end-expiratory pressure on Cerebral injury patients with hypoxemia

Xiang-yu Zhang MD?, Zi-jian Yang MD, Qi-xing Wang RRT, Hai-rong Fan MD

Department of Emergency and Critical Care Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China

Received 16 January 2010; revised 27 January 2010; accepted 28 January 2010

Abstract

Background: Traumatic brain injury or intracranial hemorrhage patients with acute lung injury/acute respiratory distress syndrome need mechanical ventilation. The use of Positive end-expiratory pressure in this situation remains controversial. This study explored the impact of PEEP on intracranial pressure , Cerebral perfusion pressure (CPP), central venous pressure , and mean arterial pressure (MAP) in cerebral injury patients.

Methods: Nine cerebral injury patients with lung injury who needed mechanical ventilation and met the criteria for ICP monitoring were included in this study. Intraventricular catheters were positioned in 1 of the bilateral ventricles and connected to pressure transducers. Invasive arterial pressure and CVP were monitored continuously. Pressure control ventilation was applied during this clinical trial in a stepwise recruitment maneuver (RM) with 3 cm H₂O intermittent increments and decrements of PEEP. Results: A total of 28 RMs were completed in 9 patients. Mean values of MAP, CVP, ICP, and CPP 5 minutes after RMs showed no significant differences compared with baseline (P N 0.05). Correlation analysis of all the mean values of MAP, CVP, ICP, and CPP showed significant correlation between MAP and CPP, PEEP and CVP, PEEP and ICP, and PEEP and CPP with all P values less than 0.05. Conclusion: The impact of PEEP on blood pressure, ICP, and CPP varies greatly in cerebral injury patients. Mean arterial pressure and ICP monitoring is of benefit when using PEEP in cerebral injury patients with hypoxemia.

(C) 2011

Traumatic brain injury or intracranial hemorrhage patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) need mechanical ventilation support. This presents a dilemma for clinical caregivers. To maintain oxygenation, it is occasionally necessary to perform lung recruitment maneuvers (RMs) [1,2], to recruit collapsed pulmonary alveoli using a high airway pressure followed by appropriate positive end-expiratory pressure (PEEP) to

* Corresponding author. Tel.: +86 21 66307174; fax: +86 21 66301051.

E-mail address: [email protected] (X. Zhang).

maintain the recruited alveoli open. However, high intratho- racic pressure impedes venous blood return to right atrium and decreases the preload, resulting in diminished cardiac output [3]. In addition, due to the impedance of venous blood flow, Intracranial pressure may be elevated and be detrimental to brain injury patients. Although a large number of experimental and clinical studies have been conducted, there is still controversy [4,5] regarding the management of Intracranial hypertension and cerebral edema when a high airway pressure is used especially with lung RM for ARDS. How to treat these patients appropriately and balance the benefits and risks is a continuing issue in clinical care. From

0735-6757/$ – see front matter (C) 2011 doi:10.1016/j.ajem.2010.01.042

Treatment regimen during study”>May 2007 to March 2008, 28 RMs in 9 brain injury patients were performed. We report the effects of RM on mean arterial pressure (MAP), central venous pressure (CVP), ICP, cerebral perfusion pressure (CPP), and the correlations between these parameters.

Methods

Subjects

Nine cerebral injury patients with lung injury who needed mechanical ventilation and met the criteria for ICP monitoring were included in this clinical trial from May 2007 to March 2008. The clinical data of these patients are shown in Table 1.

Treatment regimen during study

Lung RMs were started from PEEP of 0 cm H₂O with increments of 3 cm H₂O at an interval of 3 minutes until PEEP reached 21 cm H₂O or stopped due to patient’s intolerance according to monitoring parameters. Thereafter, PEEP level was downregulated with decrement of 3 cm H₂O at an interval of 3 minutes, and the point of PEEP level at which the oxygenation obviously decreased was recorded for later PEEP setting consideration. The corresponding values of MAP, CVP, ICP, and CPP at the end of each interval during the procedure were recorded. Fractional inspiratory oxygen (FiO2) was set to 100% during the whole process to ensure patients safety. Recruitment maneuvers were reper- formed, and PEEP was set to an appropriate level according to the former PEEP decrement titration. FiO2 was then set to an appropriate level to ensure adequate patient oxygenation. All the patients were put in supine position. Central venous catheterization and radial arterial catheterization were performed. Pressure transducers were connected to a Philips MP₅₀ monitor (Philips Medizin Systeme Boeblingen GmbH, Germany). Intraventricular catheters were inserted into 1 of bilateral ventricles during operation [6]. Ventilation was set to provide pressure control mode, an inspiratory time of 1

Table 1 Clinical data of the patients

second, a targeted tidal volume of 6 mL/kg, and a frequency of 14/min. Propofol was used to maintain the Ramsey Scale at 4 points or more during the whole course for those patients who were breathing spontaneously. vasoactive agents and fluid therapy were applied according to monitored results of CVP and MAP. Mean arterial pressure was maintained above 80 mm Hg at baseline.

Indication for ICP monitoring [7] was intracerebral hemorrhage or traumatic brain injury with a Glasgow Coma Scale score of 8 points or less. Recruitment maneuver was indicated at a PaO2/FiO2 less than 150 during mechanical ventilation support and airway management. Recruitment maneuver should be stopped and PEEP decreased if the following situations occurred: (1) transient hypotension with MAP decreases 30% of baseline or below 90 mm Hg lasting for 2 minutes and (2) transient Cerebral hypoperfusion of CPP decreases 30% of baseline or below 60 mm Hg lasting for 2 minutes. Arterial blood gas was sampled before lung RM to establish the necessity of RM and at the end of each interval of PEEP decrement to confirm the effects of RMs. Arterial blood gas was sampled again at 10 minutes after the second RM completed and ventilation stabled to estimate effectiveness of RMs. Recruitment maneuvers and each of monitoring are requested by patients’ condition and necessity of treatment. Thus, informed consent was waived. Determination of tendency of cerebral perfusion during RM and the serial MAP, CVP, ICP, and CPP were divided into 3 phases according to each of the 3 periods of changing PEEP (PEEP increasing period, the maximal level PEEP period, and PEEP decreasing period). The mean of MAP, CVP, ICP, and CPP during each phase was calculated and comparisons between any 2 mean variates of these 3 phases were performed.

Statistical analysis was conducted using an SPSS 13.0 package

(SPSS, Chicago, Ill) for correlation and variance analysis.

Results

A total of 28 RMs were completed in 9 patients. The distribution of the maximal PEEP in the completed 28 RMs is shown in Table 2. PaO2/FiO2 before and after RM were 128

+- 31 and 245 +- 35 mm Hg, respectively. Improvement is significant (P b .01). Mean values of MAP, CVP, ICP, and CPP at sequent PEEP levels are shown in Table 3. Compared with the baseline analysis of variance, no significant difference for each parameter was shown. Correlation analysis of all the mean values of MAP, CVP, ICP, and CPP showed significant correlation between MAP and CPP, PEEP and CVP, PEEP and ICP, and PEEP and CPP, with all P values less than 0.05 (Table 4). The percentile of RMs, which presented with significant correlation between any 2 variates within an individual RM to the total RMs, was as follows: (1) a positive correlation between MAP and CPP existed in 89.3% (25/28) of total RMs, (2) a positive correlation between PEEP and CVP existed in 85.7% (24/28) of total RMs, (3) a positive correlation between PEEP and ICP existed in 75.0% (21/28) of total RMs, and (4) negative correlation between PEEP and CPP existed in 60.7% (17/28) of total RMs.

Table 2 Distribution of the maximal PEEP

In 15 of 28 RM, CPP decreased when PEEP elevated and then increased when PEEP decreased and returned to baseline when PEEP returned to baseline. In 2 of 28 RMs, CPP decreased when PEEP was elevated and although rebound slowly but could not return to baseline simulta- neously when PEEP returned to baseline and needed additional 8 and 10 minutes, respectively, to return to baseline. In 11 of 28 RM, the CPP kept constant. In 21 of 28 RM, ICP increased when PEEP was elevated and then decreased when PEEP decreased. In 7 of 28 RMs, the ICP

Table 3 Mean values of MAP, CVP, ICP, and CPP at sequent PEEP levels in 30 RMs

remained constant. In 24 of 28 RMs, CVP increased to a relative high level in response to elevated PEEP and decreased when PEEP returned to baseline. In 4 of 28 RM, CVP was constant throughout.

Table 4 R values for the correlation analysis between the mean values of PEEP, MAP, CVP, ICP, and CPP

Discussion

Recruitment maneuver is a common ventilatory strategy for ALI/ARDS, which entails appropriate PEEP. In patients with brain injury and ALI/ARDS, RM may be considered for improving oxygenation [8,9]. Cerebral perfusion pressure would deteriorate due to the restriction of venous blood return to right atrium and elevation of ICP from RM.

This study has shown that changes in CPP after alteration of PEEP were diverse. Similar to our findings are in agreement with those of Muench and colleagues [10]; there is a positive correlation between CPP and MAP. It is obvious that maintaining effective MAP may ensure the safety of RM in brain injury patients [11]. Lowe and Ferguson [12] reviewed published articles and concluded that lung RMs could be safely performed in patients with both brain and lung injury, especially with a PEEP level lower than the ICP. However, in our clinical trial, CPP responded to elevation of

PEEP level in various ways. Cerebral perfusion pressure dropped to relative lower level and returned to baseline in 17 RMs when the PEEP level was increased, but CPP dropped and was maintained at relative lower level in other 2 RMs. Hence, we conclude that it is not safe to perform RM in patients with severe cerebral edema. It should be mentioned that although the average CPP during RM were not significantly altered, there was obvious alterations of CPP in individualized episodes of RM, which were not reflected from data of average CPP. It may result from episodes of RM abortion due to CPP dropping. Continuous MAP and CPP monitoring is required to ensure patient safety. In this trail, any episode of obvious decrease in MAP or CPP to lower than the safe level would require termination of RM and decreasing PEEP. If continuous MAP and CPP monitoring is not used, MAP and CPP safety cannot be ensured when RM is used in brain injury patients with ALI/ARDS.

From our data, it is evident that the tendency of ICP and CPP in response to sequent alteration of PEEP was not uniformly predictable: ICP and CPP may decrease, remain stable, or increase. Cerebral perfusion pressure in some patients did not drop significantly due to the increase in MAP when mean airway pressure increased. Long-term positive- pressure ventilation per se might induce high permeability of blood-brain barrier [13]. The serum concentration of the hormone regulating metabolism of salts and water might be altered after long-term use of high PEEP level [14], which in turn impact CPP.

The clinical trial conducted in patients with cerebral infarction by Huynh and colleagues [15] suggested that CPP would increase in response to elevation of PEEP, which is not in agreement with our findings This may be explained by the large difference in the ICP between the 2 studies. The average ICP in the study of Huynh et al was around 13 mm Hg, whereas that of our study was approximately 25 mm Hg. Intracranial pressure may interfere with the response of cerebral vasculature to MAP [16]. In mildly elevated or normal ICP, the cerebral vessels may contract in response to an increase in MAP through the autoregulation mechanism causing a decrease in ICP and in turn an increase in CPP. However, autoregulation of the cerebral vasculature would be interrupted in severe intracranial hypertension, and the compliance of cerebral tissue would decrease significantly. In these circumstances, ICP would increase in response to the elevation of MAP and the alteration of CPP would be uncertain. In our previous report in 6 severe brain injury patients accompanied by hypoxemia [17], we found and reported similar result of variable correlation between CPP and PEEP during 22 episodes of RM. It is either the phenomenon in severe brain injury patients whose Glasgow Coma Scale score ranges from 3 to 7.

The limitation of our study is not that all of RM episodes reached maximum level of PEEP (shown in Table 2). The reason of RM abortion is MAP, or CPP met the safety limits for patients. This is why these MAP, ICP, and CPP monitoring results showed no unsafe records beyond the

safety limits. However, the distribution of maximum PEEP levels that had been reached showed the potential unsafe limits of PEEP during the processes of RM in hypoxic brain injury patients. The significance for R value of the likelihood correlation is possibly a chance event due to sampling error (Table 4). Hence, 12 of correlations have a less than 95% chance of being true.

The response of ICP and CPP to lung RMs is variable due to the great difference in age and respiratory system compliance [12,18-20], which are likely to be major influencing factors. We conclude that in severe brain injury patients with ALI/ARDS, continuous MAP, ICP, and CPP monitoring during changing of PEEP or lung RM is required to monitor individual therapy and improve the safety of clinical treatment.

References

1. Haitsma JJ, Lachmann B. Lung protective ventilation in ARDS: the open lung maneuver. Minerva Anestesiol 2006;72:117-32.
2. Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, et al. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 2006;354:1775-86.
3. Mascia L, Grasso S, Fiore T, Bruno F, Berardino M, Ducati A. Cerebro-pulmonary interactions during the application of low levels of positive end-expiratory pressure. Intensive Care Med 2005;31: 373-9.
4. Wolf S, Schurer L, Trost HA, Lumenta CB. The safety of the open lung approach in neurosurgical patients. Acta Neurochir Suppl 2002; 81:99-101.
5. Bein T, Kuhr LP, Bele S, Ploner F, Keyl C, Taeger K. Lung recruitment maneuver in patients with cerebral injury: effects on intracranial pressure and cerebral metabolism. Intensive Care Med 2002;28:554-8.
6. Stocchetti N, Longhi L, Zanier ER. Intracranial pressure monitoring for traumatic brain injury: available evidence and clinical implications. Minerva Anestesiol 2008;74:197-203.
7. The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Indications for intracranial pressure monitoring. J Neurotrauma 2000;17:479-91.
8. Fan E, Wilcox ME, Brower RG, Stewart TE, Mehta S, Lapinsky SE, et al. Recruitment maneuvers for acute lung injury: a systematic review. Am J Respir Crit Care Med 2008;178:115611-63.
9. Qiu HB, Xu HY, Yang Y, Zhou SX, Chen YM, Sun HM. Effects of positive end-expiratory pressure on lung recruited volume and oxygenation in patients with acute respiratory distress syndrome. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue (Chinese) 2004;16:399-402.
10. Muench E, Bauhuf C, Roth H, Horn P, Phillips M, Marquetant N, et al. Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain Tissue oxygenation. Crit Care Med 2005;33:2367-72.
11. Lowe GJ, Ferguson ND. Lung-protective ventilation in neurosurgical patients. Curr Opin Crit Care 2006;12:3-7.
12. Georgiadis D, Schwarz S, Baumgartner RW, Veltkamp R, Schwab S. Influence of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure in patients with acute stroke. Stroke 2001;32:2088-92.
13. Stonestreet BS, McKnight AJ, Sadowska G, Petersson KH, Oen JM, Patlak CS. Effects of duration of positive-pressure ventilation on blood-brain barrier function in premature lambs. J Appl Physiol 2000; 88:1672-7.
14. Farge D, De la Coussaye JE, Beloucif S, Fratacci MD, Payen DM. Interactions between hemodynamic and hormonal modifications during PEEP-induced antidiuresis and antinatriuresis. Chest 1995; 107:1095-100.
15. Huynh T, Messer M, Sing RF, Miles W, Jacobs DG, Thomason MH. Positive end-expiratory pressure alters intracranial and cerebral perfusion pressure in severe traumatic brain injury. J Trauma 2002; 53:488-92.
16. Steiner LA, Andrews JD. Monitoring the injured brain: ICP and CBF. Br J Anaesth 2006;97:26-38.
17. Yang ZJ, Zhang XY, Shen JF, Wang QX, Fan HR, Jiang X, et al. The impact of positive end-expiratory pressure on cerebral perfusion pressure and hemodynamics in patients receiving lung recruitment

maneuver. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue (Chinese) 2008 Oct;20(10):588-91.

1. Caricato A, Conti G, Della Corte F, Mancino A, Santilli F, Sandroni C, et al. Effects of PEEP on the intracranial system of patients with head injury and subarachnoid hemorrhage: the role of respiratory system compliance. J Trauma 2005;58:571-6.
2. McGuire G, Crossley D, Richards J, et al. Effects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure. Crit Care Med 1997;25:1059-62.
3. David M, Markstaller K, Depta AL, Karmrodt J, Herweling A, Kempski O, et al. Initiation of high-frequency oscillatory ventilation and its effects upon cerebral circulation in pigs: an experimental study. Br J Anaesth 2006;97:525-32.