a b s t r a c t

Background: The effect of intravenous (IV) fluid administration type on cerebral perfusion pressure during cardiopulmonary resuscitation (CPR) is controversial. The purpose of this study was to evaluate the association between IV fluid type and CePP in a porcine cardiac arrest model.

Methods: We randomly assigned 12 pigs to the hypertonic crystalloid, isotonic crystalloid and no-fluid groups. After 4 min of untreated ventricular fibrillation (VF), chest compression was conducted for 2 cycles (CC only). Chest compression with IV fluid infusion (CC + IV) was followed for 2 cycles. Advanced life support, including defibrillation and epinephrine, was added for 8 cycles (ALS phase). Mean arterial pressure (MAP), intracranial pressure and CePP were measured. A paired t-test was used to measure the mean difference in CePP. Results: Twelve pigs underwent the experiment. The hypertonic crystalloid group showed higher CePP values than those demonstrated by the isotonic crystalloid group from ALS cycles 2 to 8. The MAP values in the hyper- tonic group were higher than those in the isotonic group starting at ALS cycle 2. The ICP values in the hypertonic group were lower than those in the isotonic group starting at ALS cycle 4. From ALS cycles 2 to 8, the reduction in the mean difference in the isotonic group was larger than that in the other groups.

Conclusion: In a VF cardiac arrest porcine study, the hypertonic crystalloid group showed higher CePP values by maintaining higher MAP values and lower ICP values than those of the isotonic crystalloid group.

(C) 2021

1. Introduction

Out-of-hospital cardiac arrest (OHCA) is a major public health con- cern with poor prognosis [1,2]. Improving organ perfusion during car- diopulmonary resuscitation (CPR) is important for increasing survival and good Neurologic recovery outcomes in OHCA [3-6]. To maintain organ perfusion, either isotonic crystalloids or colloids can be used as the initial fluid choice for resuscitation.

The burden of neurologic disability in cardiac arrest victims is high,

and neuroprotective resuscitation has been emphasized for OHCA [7-9]. Optimal cerebral perfusion pressure (CePP) is a crucial indicator to be maintained during CPR [10-13]. The deterioration of CePP by

* Corresponding author at: Department of Emergency Medicine, Seoul National University College of Medicine and Hospital, 101, Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.

E-mail address: [email protected] (K.J. Hong).

impeding systemic venous return and increased intracranial pressure could affect poor clinical outcome in OHCA [14]. Additionally, Cerebrovascular autoregulation, which prevents brain tissue damage due to decreased cerebral perfusion, could be disrupted during CPR and lead to decreased cerebral blood flow [9,15].

Intravenous access and fluid administration are important

procedures for improving organ perfusion and clinical outcomes in emergency care [16-18]. However, the current guidelines do not recom- mend or prohibit IV fluid administration during CPR in OHCA. In previ- ous studies, the association of IV fluid administration with clinical outcomes in OHCA has been controversial [19,20]. Considering the ad- verse physiologic effect of large volumes crystalloid IV infusion [21], the use of hypertonic crystalloids during CPR has been evaluated and has shown improved regional cerebral blood flow and potential neuro- logical benefits [22,23]. To measure cerebral perfusion by CePP, measur- ing ICP by trephination through the skull is required during CPR and is not feasible during routine Clinical processes.

https://doi.org/10.1016/j.ajem.2021.08.014

0735-6757/(C) 2021

In this study, we conducted a porcine cardiac arrest experimental study with different types of IV fluid infusions, including hypertonic crystalloids, isotonic crystalloids and no fluid administration, during CPR. The purpose of this study was to evaluate the association between the type of IV crystalloid and CePP during CPR in a porcine cardiac arrest Experimental model. We hypothesized that hypertonic crystalloid fluid infusion would be associated with higher CePP than isotonic crystalloid or no-fluid infusion during CPR.

1. Methods
   1. Study design and setting

We conducted a randomized large-Animal experimental study using a porcine ventricular fibrillation (VF) cardiac arrest model. This investigation was designed to compare the effects of different IV fluid administration methods for CePP during CPR in a porcine cardiac arrest model (Fig. 1). After 4 min of untreated VF, 3 phases of resuscitation were delivered. The 1st phase was the chest compression phase without IV administration or defibrillation (chest compression only phase, CC only phase), which lasted for 4 min. In the 2nd phase, chest compression and IV fluid ad- ministration were delivered for 4 min (chest compression and IV phase, CC + IV phase). In the 3rd phase, chest compression, IV fluid administra- tion, defibrillation and epinephrine were delivered for 16 min (advanced life support and IV phase, ALS phase). Defibrillation was always given first when the time points of epinephrine overlap. IV fluid administration was classified by 3 methods of infusion: 1) hypertonic crystalloid group (3% sodium chloride with 0.5 cc/kg/min), 2) isotonic crystalloid group (0.9% sodium chloride with 1 cc/kg/min) and 3) no-fluid group (0.9% sodium chloride keeping vein open state). During the CC + IV phase and ALS phase, methods of IV fluid administration were assigned to each pig randomly. Exact amount of crystalloid per each phase were pushed through syringe connected to extension line from fluid bag.

• 1. Surgical preparation

Twelve female cross-bred 13-15-week-old pigs with a mean body weight of 40 +- 3 kg were used in the study. The animals were main- tained in an accredited AAALAC International (#001169) facility in accor- dance with the Guide for the Care and Use of Laboratory Animals, 8th Edition, NRC (2010). Experiments were initiated after a day of fasting, and the pigs were initially sedated with an Intramuscular injection of tiletamine/zolazepam (Zoletil1) 2 mg/kg with xylazine (Rompun1) 2 mg/kg followed by isoflurane inhalation (2% for induction, 0.5% for main- tenance). While spontaneously breathing with sedation, endotracheal in- tubation was conducted with a size 7.5 endotracheal tube. Positive pressure ventilation was provided by a mechanical ventilator (Aespire

7100, GE Healthcare, USA). partial pressure of arterial carbon dioxide was maintained between 35 and 55 mmHg during mechanical ventilation to minimize variation of ICP by hyperventilation. A central ve- nous catheter was placed through the internal jugular vein to place a pac- ing guide-wire, which induced VF. Burr hole trephination was applied in the midline of the eyebrow and the anterior bony prominence of the skull. A pressure catheter (Millar catheter-SPR-350 s, Millar Instruments, Inc., Houston) was placed through the burr hole for ICP recording. aortic pressure was measured during the experiment by puncturing the femoral artery and placing a pressure catheter (Millar catheter-SPR-352 s, Millar Instruments, Inc., Houston). Electrocardiography, end-tidal carbon diox- ide (EtCO2) and body temperature (BT) data were also retrieved. All Physiological parameters were measured and recorded continuously by a digital recording system (Powerlab, AD instruments, Australia) and data processing software (Labchart, AD instruments, Australia).

• 1. Experimental protocol

After micromanometers were inserted into the skull, right ventricle, and aorta, VF was induced by transmitting low-voltage electricity near the right ventricular wall by pacing guide-wire. After 4 min of untreated VF, Mechanical chest compression (LUCAS-II, Physio-Control Inc., Sweden) was conducted for 2 CPR cycles during the chest compression- only phase. During the CC + IV phase, mechanical chest compression, bag-valve mask ventilation and IV fluid infusion were delivered for 2 cy- cles. During the ALS phase, we delivered mechanical chest compression, bag-valve mask ventilation, epinephrine every 4 min, defibrillation for shockable rhythm every 2 min and IV fluid infusion for 8 cycles. Three types of IV fluid infusion, namely, hypertonic crystalloid and isotonic crys- talloid, and no fluid, were randomly assigned to each pig (Hypertonic crystalloid, isotonic crystalloid and no fluid infusion groups). Unstratified block random allocation was used. IV fluid was infused via an internal jug- ular central catheter at a speed of 0.5 cc/kg/min for the hypertonic crystal- loid group and 1.0 cc/kg/min for the isotonic crystalloid group.

CPR was stopped during the experimental course if the return of spontaneous circulation (ROSC) was captured. ROSC was defined as mean arterial blood pressure over 60 mmHg for a minimum of 5 min in the presence of an organized rhythm. After ROSC, subjects were monitored for 20 min with ventilation only and sacrificed. After a total of 12 cycles of the experimental course without any ROSC, we finished the experimental protocol and sacrificed the animal.

• 1. Outcomes

We extracted the profiles of physiological parameters, including arterial blood pressure, intracranial pressure, heart rate, body temper- ature and EtCO2, which were measured continuously for the whole

Fig. 1. Course of experimental process.

VF, ventricular fibrillation; CC, chest compression; BVM, bag valve mask; IV, intravenous; ALS, advanced life support.

Bwt, body weight; SBP, systolic blood pressure; IQR, interquartile range; DBP, diastolic blood pressure; HR, heart rate; BT, body temperature; CO2, carbon dioxide; ICP, intracranial pressure; Hb, haemoglobin; LA, lactic acid; ROSC, return of sponta- neous circulation.

experimental duration. We assessed the baseline physiologic and labora- tory variables of each study subject, including physiologic parameters and blood gas analysis results, after the whole surgical preparation. Mean arterial blood pressure (MAP) was calculated from the observed pa- rameter. CePP was calculated as MAP minus ICP, continuously during all CPR cycles. Medians and interquartile ranges of MAP, ICP and CePP for the untreated VF period and every 2-min CPR cycle during the CC, CC + IV, and ALS phases were also calculated. The primary outcome of this study was CePP during each CPR cycle in different IV fluid infusion groups.

11

44

Isotonic 880

12

41.5

Hypertonic 420

150 (7.5)

99.9 (6)

109.6 (2)

36.6 (0)

18.8 (45.1)

9.5 (1.1)

129.4 (3.5)

99.9 (1.8)

113 (0)

37.8 (0)

39.4 (17.5)

37.0 (1.3)

7.518

39.3

84.6

97.3

32.3

9.9

137.5

1.5

no

7.47

47.5

97.9

97.9

34.9

9.8

134.5

1.4

no

• 1. Statistical analysis

10

41.5

Isotonic 830

105.1 (4.3)

81.7 (2.5)

114.1 (1.8)

37.0 (0)

24.9 (29.1)

6.6 (1.3)

7.491

44

286.8

99.9

33.9

10.5

141.4

1.6

no

To minimize confounding bias, the cycle at which ROSC was identi- fied and data after ROSC were excluded in analysis. Linear mixed model was used for analysis of group-time interaction in mean values of CePP during CPR cycle of CC + IV, and ALS phases. To assess the change in CePP by each fluid infusion time as the CPR time passed, we conducted a paired t-test with mean differences with 95% confidence intervals (CIs). We measured the mean difference between the CePP of each cycle during the CC + IV or ALS phase and the CePP of CC only cycle 2, which was the last phase without IV fluid infusion. We also measured the CePP mean difference of each cycle during the CC + IV or ALS phase with the preceding cycle. The sample size was calculated based on the prediction of a mean 10-mmHg difference in CePP reduction throughout the CPR cycles according to different IV fluid infusion types.

7

44

Hypertonic 132

8

44

No

-

9

41

No

-

150 (9.3)

109 (5.9)

87.9 (0)

38.6 (0)

24.3 (41.5)

3.4 (1.2)

173.9 (2.21)

125.4 (2.3)

98.8 (2.4)

37.1 (0)

22.7 (22.0)

5.8 (0.6)

98.2 (5.5)

64.9 (4.3)

153.9 (0.8)

34.7 (0)

27.4 (27.3)

20.2 (1.4)

7.444

54.2

59.5

90.7

37.5

10.4

141

2.2

no

7.433

55.4

133.2

99

37.3

10.9

140.4

2

no

1. Results

7.499

41.7

247.2

99.9

32.7

11.8

139.4

3.5

yes

A total of 12 pigs underwent experiments according to a pre- determined protocol (Fig. 1). ROSC were occurred at ALS cycle 3 in a sub- ject in the isotonic crystalloid group, and ALS cycle 2 in a subject in the hypertonic crystalloid group. Baseline characteristics, physiologic param- eters and blood gas analysis at baseline are described in Table 1. One sub- ject in the isotonic crystalloid group and one subject in the hypertonic crystalloid group achieved ROSC before finishing the whole experimental course. Mean administered volume of fluid were statistically lower in hypertonic crystalloid group in each phase, as we assigned 1 cc/kg/min of isotonic crystalloid and 0.5 cc/kg/min of hypertonic crystalloid for each group. Hypertonic crystalloid group showed lower systolic blood pressure, heart rate, body temperature and high EtCO2 and ICP, relatively. The MAP, ICP and CePP values during each CPR cycle for the no fluid, isotonic crystalloid and hypertonic crystalloid groups are described in Table 2. The no-fluid group showed the lowest CePP and MAP values in most CPR cycles. Isotonic or hypertonic crystalloid infusion had a more beneficial effect on increasing MAP than did no-fluid infusion. At the final experimental phase (ALS cycle 8), the MAP value was 6 [4] mmHg,

3

39

Isotonic 780

4

41.5

Hypertonic 420

5

42.5

Isotonic 340

6

41.5

No

-

108.5 (2.8)

62.7 (1)

77.7 (0.8)

38.0 (0)

24.0 (23.2)

9.3 (0.8)

121.8 (7.8)

85.4 (4.8)

103.1 (0)

35.8 (0)

22.0 (31.9)

12.2 (1.0)

161.9 (10)

109.8 (7)

134.3 (3)

37.3 (0)

21.2 (32.4)

6.0 (0.4)

147.3 (12.3)

101.2 (10.5)

133 (28.8)

36 (0)

19.4 (13.7)

8.6 (2.4)

7.55

37.4

232.7

99.9

33.1

8.4

142.1

1.6

no

7.561

37.9

344.3

100

34.3

14.8

139.1

1.5

no

7.498

46.9

81.6

96.7

36.7

11.4

142.4

1.7

yes

7.458

55.6

66.2

93.1

39.7

11.8

144.6

1.4

no

and the CePP value was 0 (29.6) mmHg in the no-fluid infusion group.

Compared to the isotonic crystalloid group, the hypertonic crystalloid group showed smooth decline of CePP values from CC + IV cycle 1 to the end of the experiment, but without significant group-time interaction. The MAP values in the hypertonic crystalloid group were higher than those in the isotonic group starting from ALS cycle 1, and the ICP values were lower in the hypertonic group compared to those in the isotonic group starting from ALS cycle 3. These differences resulted in a higher CePP value for the hypertonic crystalloid group after IV fluid infusion (Fig. 2).

Table 1

Baseline characteristics of study subjects.

The order of animals for experiment

1

46.5

Hypertonic 470

2

43.5

No

-

Physiologic parameter, median(IQR)

107 (3.5)

79.7 (2)

88.9 (0.8)

36.7 (0)

24.2 (24.5)

2.9 (0.8)

109.5 (3.5)

69 (4.3)

87.5 (1)

38.0 (0)

27.2 (19.6)

11.4 (0.9)

7.578

38.4

160.7

99.7

36.2

9.4

139

1.2

no

We measured the mean difference in CePP value in each CPR cycle

7.572

39

161.2

99.7

36.2

10.2

138.5

1.4

no

during the CC + IV and ALS phases compared to CC only phase cycle 2, which was the last cycle without randomized IV fluid infusion (Table 3). After ALS cycle 2 and until ALS cycle 8, the reduction in the mean difference compared to CC only phase cycle 2 was larger in the isotonic crystalloid group than in the hypertonic crystalloid group or the no-fluid infusion group (Figure AppendixAppendix). We also mea- sured the mean difference in CePP value between each CPR cycle and the preceding cycle (Fig. 3). The CePP value of the isotonic crystalloid group decreased sharply at ALS cycles 2 and 3.

Variable

Bwt, Kg Fluid type

Total fluid dose, cc

SBP (mmHg) DBP (mmHg) HR (beat/min) BT (?C)

EtCO2 (mmHg) ICP (mmHg)

Arterial blood gas analysis

pH

pCO2 (mmHg) pO2 (mmHg) SpO2 (%) HCO3 (mEq/L)

Hb (g/Dl)

Soidum (mmol/L) LA (mg/dL)

ROSC

Table 2

Cerebral perfusion pressure during CPR by each IV fluid infusion group. CPR cycle of experimental phase Type of IV fluid infusion method

No fluid infusion Isotonic crystalloid Hypertonic crystalloid

	MAP (mmHg)		ICP (mmHg)		CePP (mmHg)		MAP (mmHg)		ICP (mmHg)		CePP (mmHg)		MAP (mmHg)		ICP (mmHg)		CePP (mmHg)
	Mean (SD)		Mean (SD)		Mean (SD)		Mean (SD)		Mean (SD)		Mean (SD)		Mean (SD)		Mean (SD)		Mean (SD)
Untreated VF	18.0 (7.0)		14.0 (3.9)		4.1 (9.4)		30.2 (23.0)		14.7 (4.2)		15.5 (23.1)		21.8 (8.3)		15.2 (7.4)		6.6 (10.0)
CC only cycle 1	30.7 (11.7)		14.7 (8.8)		16.0 (17.1)		50.8 (18.3)		16.2 (5.9)		34.5 (17.6)		42.4 (8.7)		17.3 (14.4)		25.1 (13.2)
CC only cycle 2	33.4 (12.6)		11.9 (9.1)		21.6 (19.5)		52.9 (25.2)		15.4 (6.2)		37.5 (23.3)		41.0 (6.0)		15.1 (11.4)		26.0 (9.5)
CC + IV cycle 1	26.9 (8.1)		9.1 (8.6)		17.8 (15.0)		50.8 (25.4)		13.3 (5.8)		37.4 (24.4)		36.8 (6.6)		13.0 (8.9)		23.7 (9.0)
CC + IV cycle 2	25.4 (12.2)		7.2 (9.4)		18.2 (20.8)		44.2 (27.3)		11.5 (5.4)		32.7 (27.7)		32.4 (4.8)		11.1 (8.3)		21.2 (7.3)
ALS cycle 1	24.2 (13.0)		5.1 (11.4)		19.1 (22.6)		41.2 (31.0)		10.1 (5.3)		31.0 (32.6)		32.9 (7.2)		10.5 (8.4)		22.4 (7.7)
ALS cycle 2	22.2 (11.6)		4.9 (10.4)		17.3 (18.7)		22.6 (15.3)		10.0 (5.5)		12.6 (19.4)		33.3 (5.9)		12.0 (8.1)		21.3 (8.5)
ALS cycle 3	12.6 (5.6)		2.9 (11.6)		9.7 (10.1)		16.3 (6.5)		12.2 (1.8)		4.1 (7.6)		29.5 (13.3)		12.9 (7.5)		16.6 (8.7)
ALS cycle 4	10.9 (5.8)		2.0 (12.2)		8.9 (7.6)		15.9 (6.1)		12.3 (1.3)		3.6 (6.8)		23.4 (9.7)		12.1 (6.7)		11.3 (3.7)
ALS cycle 5	8.0 (4.0)		0.9 (13.5)		7.1 (10.0)		14.5 (5.1)		11.7 (1.6)		2.8 (6.3)		21.5 (9.1)		7.5 (9.8)		14.0 (8.1)
ALS cycle 6	6.1 (13.6)		1.0 (14.3)		5.2 (16.2)		14.4 (5.2)		11.8 (1.6)		2.6 (6.3)		18.8 (8.4)		6.0 (10.0)		12.8 (8.0)
ALS cycle 7	6.7 (3.2)		-0.3 (15.4)		6.9 (13.1)		13.8 (4.4)		11.7 (1.6)		2.1 (5.5)		16.1 (7.2)		5.4 (9.1)		10.7 (6.5)
ALS cycle 8	6.3 (2.3)		-0.7 (15.1)		7.0 (13.4)		12.9 (3.0)		12.9 (1.6)		0.0 (3.7)		13.2 (6.2)		5.4 (9.0)		7.8 (5.2)

MAP, mean arterial pressure; ICP, intracranial pressure; CePP, cerebral perfusion pressure; SD; standard deviation; VF, ventricular fibrillation; EMS, emergency medical service; CC, chest compression; IV, intravenous; ALS, advanced life support.

There were no significant adverse events during the whole course of the experiment.

1. Discussion

We conducted a porcine cardiac arrest experimental study to inves- tigate the effect of different IV fluid infusion types on CePP during CPR. The hypertonic or isotonic crystalloid IV fluid infusion group showed a benefit in maintaining higher MAP values compared to the no-fluid in- fusion group. In the comparison between hypertonic crystalloid infu- sion and isotonic crystalloid infusion, the hypertonic crystalloid infusion group showed higher CePP values than those of the isotonic crystalloid infusion group.

As the CPR time passed after entering CC + IV cycle 2, the MAP values became higher and the ICP values became lower in the hypertonic group than in the isotonic group. In particular, a sharp decline in CePP values in the isotonic crystalloid group was observed in the middle of the experi- mental course, including CC + IV cycle 2 and ALS cycle 1,2. A previous study investigated the clinical outcomes of hypertonic or isotonic IV fluid infusion during CPR [24-26]. In this study, we measured cerebral perfusion status by CPR continuously during CPR as resuscitation time passed. Hyper- tonic crystalloid infusion showed a beneficial effect in maintaining a higher CePP value compared to other IV fluid infusions during CPR.

Hypertonic crystalloid infusion has been investigated as a treatment

to provide clinical benefits in cardiac arrest. Hypertonic fluid could im- prove microlevel tissue perfusion [25,27] and concurrent volume ex- pansion [22]. Previous studies have focused on the effect of reinforcing Myocardial blood flow [24]. Hypertonic crystalloids have been found to reduce leukocyte-endothelial interactions and perivascular swelling

[28] and could improve vital organ perfusion, including for the brain. Several experimental studies have compared hypertonic fluid to iso- tonic fluid in terms of regional blood flow and tissue perfusion [29- 32]. Although haemodynamic and biochemical findings support the po- tential benefit, clinical trials have not clarified a definite relationship. Few studies have been conducted that measure the effect of hypertonic and isotonic crystalloids on CePP during CPR. In this study, hypertonic crystalloids showed a beneficial effect in maintaining MAP values with- out increased ICP values compared to the no-fluid or isotonic crystalloid group. This effect results in a higher CePP value than that of other fluid groups over CPR time. The effect of each type of fluid management on maintaining CePP during ongoing CPR can be clarified by mean differ- ence calculation. Based on the results, the CePP value rapidly deterio- rated after 4 to 8 cc per kilogram of isotonic crystalloid infusion.

ICP values increased immediately after cardiac arrest, depending on the filling pressure of the circulation [33]. Venous congestion in the jug- ular vein increased ICP values and could be aggravated by IV fluid ad- ministration. A steeper negative ICP slope during CPR was associated with a higher Quality of CPR by augmenting negative intrathoracic pres- sure [11]. Different effects of each IV fluid infusion on ICP values were observed in this investigation (Fig. 2). Hypertonic crystalloids do not delay ICP decline compared to isotonic crystalloids. It can be assumed that promoting water flow across the brain-blood barrier based on os- motic gradient differences countervails the venous congestion effect, which is supposed to be lower than that of isotonic fluid [34]. Krep et al. demonstrated that cerebral blood flow, which is the other deter- mining factor for cerebral perfusion, was higher during CPR with hyper- tonic crystalloid [23]. Based on results of our study, it can be assumed that the effect of reducing ICP enhances cerebral perfusion and en- hances blood flow.

To reflect the actual situation at the scene of OHCA, we designed 3 ex- perimental phases. After untreated VF, a 4-min chest compression cycle was designed assuming bystander CPR by the layperson after EMS activa- tion. Chest compression IV cycle and advanced life support IV cycle reflect prehospital care by EMS provider at the scene. Based on the results of our study, routine IV infusion of isotonic crystalloids could be harmful for ac- quiring optimal cerebral perfusion in OHCA. On the other hand, hyper- tonic fluid could improve perfusion of vital organs and prevent CePP deterioration. To implement this result in prehospital practice, further clinical study is required. In a previous study, Prehospital use of hyper- tonic crystalloid IV infusion was associated with higher ROSC and Survival to admission [35]. Since hypertonic crystalloid showed association with favorable CePP in our experiment, good neurologic recovery would be ob- tained with sufficient sample size. However, the proper density and amount of hypertonic fluid was not certain in the study. It should be care- fully approached since hypernatremia can adversely affect after ROSC [36]. Considering trends of CePP between isotonic and hypertonic crystal- loid, changing type of fluid administration during CPR could be an option reducing side effects [37]. Prehospital implementation of hypertonic crys- talloids also showed various clinical outcomes in different diseases, such as traumatic brain injury or traumatic shock [38,39].

• 1. Study limitations

There are several limitations present in this study. First, we did not measure right atrial pressure, which is needed to calculate coronary perfusion pressure; rather, we used intrajugular central catheterization to infuse intravenous fluid during CPR. We assumed that measuring

Fig. 2. Physiologic parameters by intravenous fluid type through experimental phases.

CePP, cerebral perfusion pressure; MAP, mean arterial pressure; ICP, intracranial pressure; VF, ventricular fibrillation; CC, chest compression; IV, intravenous; ALS, advanced life support.

Table 3

Difference in cerebral perfusion pressure in each CPR cycle with IV fluid infusion compared to the phase without IV fluid infusion.

CPR cycle of experimental phase	Type of IV fluid infusion method
	No fluid infusion mean (95% CI)	Isotonic crystalloid mean (95% CI)	Hypertonic crystalloid mean (95% CI)
CC + IV cycle 1	-4.1 (-6.3/-1.8)	-0.3 (-3.5/2.9)	-2.2 (-3.4/-1.1)
CC + IV cycle 2	-3.6 (-6.1/-1.1)	-4.7 (-8.0/-1.41)	-4.7 (-5.8/-3.7)
ALS cycle 1	-2.5 (-5.2/0.2)	-6.7 (-10.4/-3.1)	-3.5 (-4.6/-2.5)
ALS cycle 2	-4.2 (-6.6/-1.8)	-25.0 (-27.8/-22.3)	-5.1 (-6.4/-3.7)
ALS cycle 3	-11.8 (-13.8/-9.8)	-34.5 (-37.1/-31.9)	-8.8 (-10.1/-7.4)
ALS cycle 4	-12.8 (-14.7/-10.9)	-32.6 (-35.1/-30.1)	-14.6 (-15.7/-13.5)
ALS cycle 5	-14.5 (-16.6/-12.4)	-35.1 (-37.7/-32.6)	-11.9 (-13.2/-10.5)
ALS cycle 6	-16.4 (-18.6/-14.2)	-36.1 (-38.7/-33.6)	-13.1 (-14.4/-11.7)
ALS cycle 7	-14.3 (-16.4/-12.2)	-34.5 (-36.9/-32.1)	-15.4 (-16.6/-14.2)
ALS cycle 8	-14.7 (-16.9/-12.5)	-38.5 (-41.0/-35.9)	-18.7 (-19.8/-17.5)

CI, confidence interval; CC, chest compression; IV, intravenous; ALS, advanced life support.

Fig. 3. Reduction of cerebral perfusion pressure during each CPR cycle compared to the preceding CPR cycle according to type of IV fluid infusion. CI, confidence interval; CC, chest compression; IV, intravenous; ALS, advanced life support.

right atrial pressure via an internal jugular catheter with concurrent fluid infusion would be inaccurate. Next, there were individual varia- tions of baseline physiologic parameters including MAP, ICP and PaCO2. 5 pigs showed PaCO2 over 45 mmHg, but there was no sub- ject with acidosis. Although it may not significantly affect the exper- imental results since all study subjects were induced VF after the baseline phase, it is also a limitation. Third, the results from 0.9% so- dium chloride and half dose of 3% sodium chloride cannot be gener- alized to all kinds of crystalloids. We assumed that intravascular Volume expansion effect of 3% sodium chloride would be similar to that of 0.9% sodium chloride. They belong to the most easily encoun- tered crystalloid, it is another significant limitation. Next, electrolyte imbalance caused by IV crystalloids was possible. Such an electrolyte imbalance could affect clinical outcomes, such as ROSC, but this study focused on CePP during CPR as the primary outcome. Fifth, the histo- logical findings of brain tissue and neurologic recovery were not evaluated in this study. Finally, this study was a large-animal exper- imental study design. Thus, it has a limitation of direct generalization to humans.

1. Conclusion

In a porcine model of VF cardiac arrest, isotonic crystalloid IV admin- istration was associated with a larger reduction in CePP values during CPR compared to hypertonic crystalloid administration. The hypertonic crystalloid group showed higher CePP values, which were obtained by maintaining higher MAP values and lower ICP values than those of the isotonic crystalloid group as the CPR time elapsed.

Disclaimer

The protocol of this study was approved by the Institutional Animal Care and Use Committee of the study institution (IACUC No. 19-0175- S1A0).

Acknowledgement

This study had no conflict of interest. This investigation was supported by the Research Fund of the Study Institution (Grant No. 04-2019-0730).

Appendix

Fig. A-1. Reduction in cerebral perfusion pressure during each CPR cycle with IV fluid infusion compared to the phase without IV fluid infusion according to the type of IV fluid.

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