Intensive Care Med (2011) 37:147155

DOI 10.1007/s00134-010-2006-2

Jesus Lopez-Herce
Barbara Fernandez
Javier Urbano
Santiago Menca
Maria Jose Solana
Antonio Rodrguez-Nunez
Jose Mara Bellon
Angel Carrillo

Received: 7 March 2010

Accepted: 9 June 2010
Published online: 14 September 2010
Copyright jointly held by Springer and
ESICM 2010

EXPERIMENTAL

Hemodynamic, respiratory, and perfusion

parameters during asphyxia, resuscitation,
and post-resuscitation in a pediatric model
of cardiac arrest

J. M. Bellon
Preventive and Quality Control Service,
Hospital General Universitario Gregorio
Maranon, Madrid, Spain

Abstract Purpose: To analyze the

evolution of hemodynamic, respiratory, and tissue perfusion parameters
in an infant animal model of
asphyxial cardiac arrest (CA). Methods: This was a secondary analysis
of a prospective observational study
conducted at a laboratory research
department of a university hospital.
J. Lopez-Herce ())
B. Fernandez

Seventy-one, 2-month-old piglets
J. Urbano
S. Menca
M. J. Solana

were studied. CA was induced by
A. Carrillo
removal of mechanical ventilation.
Pediatric Intensive Care Service,
Cardiopulmonary resuscitation (CPR)
Hospital General Universitario
was performed by means of manual
Gregorio Maranon, Dr Castelo 47,
external chest compressions,
28009 Madrid, Spain
e-mail: pielvi@ya.com
mechanical ventilation, epinephrine
Tel.: ?34-91-5290308
and/or terlipressin intravenous
Fax: ?34-91-5868018
administration. Results: The evolution of hemodynamic (heart rate,
J. Lopez-Herce
B. Fernandez

blood pressure, cardiac index), respiJ. Urbano
S. Menca
M. J. Solana

ratory (end-tidal CO2, blood gas
A. Carrillo
analysis), and tissue perfusion (intraSpanish Health Institute Carlos III,
Maternal, Child Health and Development
mucosal gastric pH, central, cerebral,
Network, Santiago de Compostela, Spain
and renal hemoglobin saturation)
parameters was analyzed during three
A. Rodrguez-Nunez
periods: asphyxia, CPR, and after
Pediatric Emergency and Critical Care
Division, Hospital Clnico Universitario de return of spontaneous circulation
(ROSC). During asphyxia, a severe
Santiago de Compostela, Santiago de
arterial and tissue hypoxia with
Compostela, Spain
Electronic supplementary material
The online version of this article
(doi:10.1007/s00134-010-2006-2) contains
supplementary material, which is available
to authorized users.

hypercapnia and lactic acidosis

quickly developed. Bradycardia,
hypotension, and increasing of systemic vascular resistances and
pulmonary arterial pressure were also
observed. During CPR, arterial,
cerebral, and tissue oxygenation were
low in spite of ventilation with oxygen 100%. After ROSC a rapid
restoration of hemodynamic and
respiratory parameters was observed.
However, 30 min after ROSC, lactic
acidosis and low intramucosal gastric
pH persisted. Conclusions: Asphyxia leads to sudden
hypoxia and hypercapnia with tissue
hypoxia and progressive bradycardia.
Standard CPR is not able to maintain
an adequate tissue oxygenation during CPR in this animal model. When
ROSC is achieved, a rapid restoration
of the normal values of general
hemodynamic and respiratory
parameters is observed, although
lactic acidosis and splanchnic hypoperfusion persist in time.
Keywords Cardiac arrest

Respiratory arrest
Children

Asphyxia
Tissue perfusion

Cardiopulmonary resuscitation

Advanced life support

Post-resuscitation

148

Introduction
In cardiac arrest (CA), several factors, etiology, type of
arrest, age, previous patients status, ECG rhythm, time
elapsed from the arrest to start of CPR, and quality of
CPR have been implicated in the response to CPR and
final outcome [18].
Data about the pathophysiology of CA in children are
very scarce and most knowledge of the hemodynamic,
respiratory, and tissue perfusion events during CA and
CPR come from animal studies. However most experimental CA studies in animals have been done in adult
models that employ induced ventricular fibrillation in adult
animals. These models are not adequate to study CA in
children, because in this age group respiratory diseases and
trauma are the leading causes of CA [3, 5, 6, 9, 10]. In such
circumstances CA follows an episode of asphyxia due to
apnoea or progressive hypoventilation. Few investigations
have studied CA in pediatric animal asphyxial models and
these did not assess in detail the evolution of hemodynamic, respiratory, and metabolic parameters [11, 12].
Therefore, the objective of this secondary analysis of a
previously published prospective study [13] was to analyze, in an infant animal model, the hemodynamic,
respiratory, and tissue perfusion/oxygenation response to
hypoxia leading to CA, during CPR and after ROSC.

Materials and methods

International guidelines for the care of experimental animals were applied throughout the study; the experimental
protocol was approved by the local institutional ethical
animal investigation committee. Seventy-one healthy
2- to 3-month-old Maryland pigs with a mean (SD)
weight of 9.1 (2.2) kg were used.
Initial anesthesia was performed with intramuscular
administration of ketamine and atropine, followed by
propofol, fentanyl, and atracurium for oral endotracheal
intubation with a cuffed tube.
Mechanical ventilation was provided by a Drager
SA2, Babylog ventilator (N, Lubeck, Germany) with a
respiratory rate of 20 breaths per minute, tidal volume of
10 ml/kg, FiO2 of 50%, and positive end-expiratory
pressure (PEEP) of 3 cmH2O. Ventilation was adjusted to
achieve an end-tidal CO2 (EtCO2) from 33 to 35 mmHg
and PaCO2 from 35 to 45 mmHg.
Sedation and muscle relaxation (propofol 10 mg/kg/h,
fentanyl 10 mcg/kg/h, and atracurium 2 mg/kg/h intravenous continuous infusion) was maintained throughout
the procedure, in order to avoid the presence of spontaneous respirations. Monitoring included ECG, peripheral
arterial hemoglobin oxygen saturation (Visconnet monitor, KGB Madrid, Spain), cerebral (in the middle of the
cranium), and renal (in the renal fosa) hemoglobin oxygen

saturation by near-infrared spectroscopy (INVOS Cerebral Oximeter monitor, Somanetics, Troy, Mi, USA) after
skin shaving, and the respiratory volumes and pressures,
FiO2, end-tidal CO2 (EtCO2), by means of a spirometer
connected to the endotracheal tube and an S5 monitor
(Datex Ohmeda, Madison, USA). A 4-F PiCCO catheter
was inserted into the femoral artery to measure the blood
pressure and cardiac output (CO) by means of a femoral
arterial thermodilution system (PiCCO, Pulsion Medical
Systems, Munich, Germany). A 5-F catheter was placed
through the external jugular vein to measure the central
venous pressure (CVP), a 5.5-F Swan-Ganz catheter
(Vigilance; Edwards Lifesciences, Irving, USA) was
inserted via the femoral vein to monitor the pulmonary
arterial pressure (MPAP) and to measure CO by means
pulmonary arterial thermodilution. To measure gastric
intramucosal pH (pHi), a 7-F tonometric catheter (TRIP,
Tonometrics Division, Instrumentarium Corp, Helsinki,
Finland) was inserted in the stomach and connected to a
S5 monitor (Datex-Ohmeda Madison, USA).
Blood gases were analyzed by using the GEM Premier
3000 blood gas analyzer (Instrumentation Laboratory, Lexington, USA). Also, standard hemogram and
determination of aminotransferase (AST), alanine aminotransferase (ALT), and troponin were performed.
When baseline data were collected, CA was induced by
disconnection from the respirator for at least 10 min. After
this time, CA (defined as a heart frequency less than
60 beats per minute and systolic arterial pressure less than
30 mmHg) was confirmed and then CPR was started.
Initial CPR was performed by means of continuous
manual external chest compressions (at rate of 100 compressions/minute) and mechanical ventilation (20 breaths
per minute [bpm] with 100% oxygen). Quality of chest
compressions was monitored by the analysis of pulse
pressure arterial wave in the monitor. After 3 min of CPR,
data were collected and the return of spontaneous circulation (ROSC) was checked. At that time, the animals
without ROSC were randomly distributed into four study
groups: adrenaline standard dose (Asd): 0.01 mg/kg/
3 min; adrenaline high dose (Ahd): first standard dose
(0.01 mg/kg) followed by subsequent high doses
(0.1 mg/kg/3 min); terlipressin (T): 20 mcg/kg/6 min;
and adrenaline standard plus terlipressin (Asd ? T). In all
cases, bicarbonate was administered after 9 and 18 min of
CPR. The data comparing the ROSC between the four
therapeutics groups have been previously published [13].
CPR was stopped when ROSC was obtained or after
20 min. After ROSC, mechanical ventilation was maintained with 100% oxygen and adjusted to obtain arterial
PCO2 from 35 to 45 mmHg (4.7 to 6 kPa).
The following parameters were recorded at baseline
and every 3 min during the resuscitation: inspiratory tidal
volume, EtCO2, mean arterial pressure (MAP), CVP,
mean pulmonary arterial pressure (MPAP), peripheral
hemoglobin oxygen saturation, and cerebral and renal

149

hemoglobin saturation. CO measurements were performed

simultaneously by means of pulmonary and arterial thermodilution, and secondary parameters were registered (CI,
cardiac index; SVRI, systemic vascular resistance index;
SVI, stroke volume index; ITBI, intrathoracic total blood
index; GEDVI, global end-diastolic volume index; ELWI,
extravascular lung water index; DPmax, left ventricular
contractility; SVV, systolic volume variation). Arterial
and venous blood gases and lactate measurement was also
performed every 5 min. Five, 15 and 30 min after ROSC,
hemodynamic and analytical data were collected. Blood
temperature was continuously recorded by the intra-arterial catheter and was maintained between 34 and 35C
throughout the experiment.
Study data collection was stopped 30 min after ROSC.
On completion of the experiment, all successfully resuscitated animals were euthanized by the administration of
sedative overdose (propofol 20 mg/kg) and the intravenous injection of potassium chloride (20 mmol). Figure 1
summarizes the experimental protocol.
The statistical analysis was performed by using the
SPSS (version 16.0). Pearsons chi-squared test was used
for qualitative variables analysis, and Fishers exact test
when n was less than 20 or when any value was less than
5. Students t test was used to compare quantitative
variables between independent groups and the Mann
Whitney U test for variables not adjusted to the normal
distribution. Analysis of variance for repeated measurements (ANOVA) test was used to study the evolution of
the parameters during the experiment. A p value of less
than 0.05 was considered to be significant.

Cardiovascular parameters
Immediately after disconnection from the ventilator, a
sudden hypercapnia and hypoxia developed associated
with tachycardia, transitory hypertension, and increase of
peripheral vascular resistance.
However, 5 min later heart rate, blood pressure, and
CI had decreased with increase of MPAP and CVP. No
changes of systolic volume were observed but left ventricular contractility increased at 5 min and decreased
thereafter. Also, a non-significant decrease of intrathoracic blood volume and an increase of ELWI were
observed.
Respiratory parameters
The venous and arterial blood gas analysis showed a pH
decrease mainly during the first 5 min of asphyxia that
was related to a high PaCO2 increase and to a slight HCO3
decrease. PaO2 and hemoglobin oxygen saturation
decreased significantly during the 5 min of disconnection,
but changes were not significant between 5 and 10 min of
asphyxia. EtCO2 was undetectable from the moment of
disconnection.
Metabolic and perfusion parameters
Base excess, lactate, and K? increased. Transcutaneous,
renal, and cerebral oxygenation, as well as gastric pHi,
decreased. The analyzed data were similar in the four
therapeutic groups (data not shown).

Results
CPR period

Asphyxial period

Evolution of parameters during asphyxia is summarized Evolution of parameters during cardiopulmonary resuscitation is summarized in Table 2.
in Table 1.
Fig. 1 Experimental protocol

CPR period
(maximum 21)
A1: adrenaline 0,01 mg/kg
A2: adrenaline 0,01-0,1 mg/kg
T: terlipressin 20 mcg/kg
A+T: adrenaline 0,01 mg/kg +
terlipressin 20 mcg/kg

Asphyxial
period

AS
0

AS
5

Blood analysis
0, 5, 10 min

I Final of the experience

MV disconecction

Monitorization
Anaesthesia

Experimental timeline

POST ROSC period

Yes
ROSC

NO
AS
10

CPR CPR CPR CPR CPR CPR CPR

3
12
15
18 21
6
9

Blood analysis
3, 6, 12, 18 min

ROSC
5

ROSC
15

Blood analysis
ROSC, 5, 15, 30 min

ROSC
30

150

Table 1 Evolution of parameters during asphyxia (median and interquartile range) (n = 71)
Parameter

Basal

HR (beats per min)

MAP (mmHg)
CVP (mmHg)
PCP (mmHg)
MPAP (mmHg)
CI (l/min/m2)
SVRI (dyn 9 cm5/m2)
SVI (ml/m2)
DPmax (mmHg/s)
ITBI (ml/m2)
GEDVI (ml/m2)
ELWI (ml/m2)
SVV (%)
PaO2 (mmHg)
Peripheral saturation (%)
Cerebral saturation (%)
Renal saturation (%)
Arterial saturation (%)
Venous saturation (%)
Arterial pH
Venous pH
pHi
PaCO2 (mmHg)
EtCO2 (mmHg)
Gastric PCO2 (mmHg)
Arterial HCO3 (mmol/l)
Arterial BE
Lactic acid (mmol/l)
K? (mmol/l)

118
89
8
10
19
4.8
1,423
40
970
608
452
17
13.4
180
99
58
61
100
79.2
7.40
7.35
7.21
40
36
9.8
26.3
2.2
0.8
3.8

(102137)
(76100)
(68)
(713)
(1124)
(45.7)
(1,0571,647)
(34.545.4)
(7351,370)
(477760)
(357605)
(1324)
(9.818)
(121214)
(99100)
(50.568.5)
(57.563)
(99100)
(66.585.7)
(7.347.45)
(7.297.39)
(7.147.27)
(34.545)
(31.740)
(6.910.9)
(21.728.9)
(-3.64.6)
(0.51.1)
(3.44.2)

5 min

10 min

80 (65.5111)
40 (3055)
14 (816.7)
15 (8.522.5)
31 (1737.5)
3.5 (2.35.1)
755 (478.5998.5)
40.7 (1457)
1,450 (6501,775)
453 (354675)
322 (273533)
18.5 (1529)
13.3 (6.516.6)
10 (616.5)
46.5 (15.763.5)
31 (23.542)
44 (3748)
6 (3.415)
8 (418)
7.16 (7.087.24)
7.17 (7.087.24)
7.19 (7.027.22)
67 (5983)
0
10.4 (8.912.1)
26.2 (22.727.9)
-3 (-6.3 to -1.1)
4.3 (25.8)
5.8 (4.47)

50 (068.5)
0 (014)
12.5 (716.2)
NM
NM
NM
NM
NM

0.0001
0.0001
0.0001
0.111
0.05
0.001
0.009
0.840
0.012
0.166
0.143
0.012
0.873
0.0001
0.001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.018
0.0001
0.0001
0.003
0.0001

Cerebral and renal oxygenation were monitored by near-infrared

spectroscopy (NIRS)
NM not measured because monitors did not detect this parameter,
HR heart rate, MAP mean arterial pressure, CVP central venous
pressure, MPAP mean pulmonary arterial pressure, CI cardiac

NM
NM
NM
NM
NM
25 (2033)
38 (3144)
8 (519)
14 (720)
7.09 (7.057.14)
7.07 (7.067.19)
7.0 (6.867.11)
81 (7094)
0
NM
24.9 (22.625.7)
-5.1 (-9.2 to -3.6)
5.7 (3.36.8)
5.8 (57.4)

0.0001
0.0001

index, SVRI systemic vascular resistance index, SVI stroke volume

index, ITBI intrathoracic total blood index, GEDVI global enddiastolic volume index, ELWI extravascular lung water index, SVV
systolic volume variation, a arterial, pHi gastric intramucosal pH,
EtCO2 end-tidal CO2, BE base excess

Table 2 Evolution of parameters during cardiopulmonary resuscitation (median and interquartile range) (n = 45)

HR (beats per min)

MAP (mmHg)
CVP (mmHg)
CI (l/min/m2)
SVRI (dyn 9 cm5/m2)
SVI (ml/m2)
DPmax (mmHg/s)
PaO2 (mmHg)
Cerebral saturation (%)
Renal saturation (%)
Arterial saturation (%)
Arterial pH
Venous pH
pHi
PaCO2 (mmHg)
Arterial HCO3 (mmol/l)
Arterial BE
Lactic acid (mmol/l)
K? (mmol/l)

3 min

6 min

12 min

18 min

0 (00)
23.5 (17.830.3)
12 (10.517.5)
4.7 (2.47.5)
399 (23636)
34.9 (11.158.8)
840 (5751,465)
34 (24.870.3)
29 (2037)
38 (30.844.5)
69.6 (43.593.1)
7.26 (7.137.34)
7.12 (7.027.14)
7.11 (6.877.24)
31.8 (20.356.3)
16.7 (10.719.7)
-9.6 (-13.5 to -7.8)
NM
6.9 (6.69.6)

0
27
11
3.4
645
31.7
920
42
35
41
60
7.13
7.05
6.9
55.7
19.1
-9.7
6.3
7.7

0
22
14
2
611
16.9
880
44
29.5
41
62.2
7.22
7.08
6.79
67.5
26.2
-0.3
8.5
8

0
25.5
12.5
2.9
444
30.1
1,060
36
37
41
60
7.24
7.11
6.67
79.5
24.6
-2.4
9
8.3

0.172
0.521
0.322
0.753
0.615
0.753
0.852
0.034
0.307
0.431
0.247
0.032
\0.001
0.072
0.032
0.001
0.003
\0.001
0.595

(00)
(2034)
(8.816.5)
(2.26.1)
(307865)
(1891)
(6901,445)
(3453.3)
(23.540.5)
(3345)
(50.380.5)
(7.057.2)
(6.987.1)
(6.697.06)
(43.370.3)
(16.820.7)
(-12.1 to -8.4)
(4.788.4)
(6.19.1)

(00)
(1726.5)
(917)
(1.53.7)
(281899)
(11.938.2)
(4501,440)
(31.855.3)
(22.354)
(38.843.8)
(45.588.5)
(7.17.31)
(7.037.15)
(6.737.14)
(4482.3)
(17.334.1)
(-10.56.8)
(6.310.3)
(610)

(00)
(17.329)
(10.318.5)
(2.25.3)
(195946)
(20.657.1)
(5701,580)
(2954.5)
(22.544.5)
(37.548)
(3690)
(7.087.42)
(7.017.21)
(6.586.89)
(55.591.3)
(1938.6)
(-9.510.4)
(7.0511.1)
(6.39.6)

Cerebral and renal oxygenation were monitored by near-infrared SVI stroke volume index, a arterial, pHi gastric intramucosal pH,
EtCO2 end-tidal CO2, NM not measured
spectroscopy (NIRS)
HR heart rate, MAP mean arterial pressure, CVP central venous
pressure, CI cardiac index, SVRI systemic vascular resistance index,

151

ROSC period

Cardiovascular parameters

During CPR, despite a stable chest compression rate, a Evolution of parameters after ROSC is summarized in
progressive decrease of MAP and CI, without changes of Table 3.
the other hemodynamic parameters, was observed.
Cardiovascular parameters
Respiratory parameters
Arterial PaO2 and hemoglobin oxygen saturation, as well
as venous, cerebral, and renal hemoglobin oxygen saturation, remained low during CPR, despite resuscitation
with 100% oxygen. On the other hand, PaCO2 increased
progressively and EtCO2 decreased.

ROSC was observed in 26 animals. After ROSC, CI, heart

rate, DPmax, and CVP were initially increased and progressively decreased, while MAP and SVRI increased
slightly at 5 min and decreased thereafter. No statistically
significant differences were observed when parameters
were analyzed in this period. ELWI was very high at the
beginning of this period and progressively decreased to
values similar to baseline.

Metabolic parameters
Respiratory parameters
Arterial pH and bicarbonate increased and BE decreased
due to the bicarbonate administration after 9 min of CPR.
However, venous pH and pHi did not change significantly
and lactate increased but non-significantly.
When the four therapeutic groups were compared, no
significant differences between analyzed parameters were
observed.

PaO2 and hemoglobin oxygen saturation at arterial,

cerebral, and renal levels increased slightly at 5 min,
without further changes. Venous hemoglobin saturation
increased at 5 min and decreased at 30 min. PaCO2
slightly decreased, while a significant decrease of EtCO2
was observed.

Table 3 Evolution of parameters after ROSC (n = 26)

Parameter

ROSC

5 min

HR (beats per min)

MAP (mmHg)
CVP (mmHg)
CI (l/min/m2)
SVRI (dyn 9 cm5/m2)
SVI (ml/m2)
DPmax (mmHg/s)
ITBI (ml/m2)
GEDVI (ml/m2)
ELWI (ml/m2)
SVV (%)
PaO2 (mmHg)
Cerebral saturation (%)
Renal saturation (%)
Arterial saturation (%)
Venous saturation (%)
Arterial pH
Venous pH
pHi
PaCO2 (mmHg)
EtCO2 (mmHg)
Gastric PCO2 (mmHg)
Arterial HCO3 (mmol/l)
Arterial BE
Lactic acid (mmol/l)
K? (mmol/l)

152
93
10
5.08
1,407
32.5
1,370
445
351
32.5
13.7
75.5
48
49
93
75.4
7.19
7.15
6.93
48.8
43
9.9
19.3
-9.3
6.1
4.6

144
105
8
4.78
1,923
27.7
1240
553
430
25
8.6
238
59.5
54.5
100
89.4
7.15
7.14
6.96
47
40
9.3
17.8
-11.4
6.2
3.7

(137.5172.5)
(75.5113)
(612)
(37.3)
(8822,100)
(15.548.6)
(8351,765)
(402621)
(313500)
(15.837.8)
(7.118)
(54.8218)
(3568)
(4452)
(82.599.7)
(52.391.2)
(7.117.27)
(7.067.22)
(6.757.2)
(31.159.8)
(34.349)
(7.316.5)
(13.120.8)
(-14.17.6)
(2.610.4)
(3.75.6)

(133175.5)
(96128)
(5.712.2)
(3.46.0)
(1,2772,390)
(21.137.6)
(9901,555)
(416682)
(313546)
(17.830.3)
(6.111.1)
(63.5284)
(39.879.8)
(4960.5)
(86.8100)
(59.793)
(7.067.24)
(77.24)
(6.747.16)
(39.356)
(2946.5)
(7.717.5)
(14.919.4)
(-15.9 to -9.1)
(2.68.9)
(3.24.3)

Cerebral and renal oxygenation were monitored by near-infrared

spectroscopy (NIRS)
HR heart rate, MAP mean arterial pressure, CVP central venous
pressure, CI cardiac index, SVRI systemic vascular resistance index,

15 min

30 min

130.5
88
7
4.3
1,511
30
780
533
425
18
11.2
207
55
55
99.9
83.5
7.22
7.18
6.96
43
33
10.5
18.3
-9.3
5.1
3.4

123.5
87
6.5
4
1,592
32.4
690
521
395
16
12.5
197
53
55
99.9
73
7.26
7.21
6.96
42
27
9.9
19.4
-7.7
3.8
3.2

\0.001
0.001
\0.001
0.021
0.954
0.019
\0.001
0.050
0.050
0.448
0.522
0.023
0.065
0.009
0.022
0.029
0.173
0.572
0.954
0.619
0.014
0.550
0.624
0.035
0.020
0.122

(115.3148.8)
(73107.8)
(510)
(3.55.2)
(1,2951,889)
(21.740.6)
(6151,155)
(439723)
(343576)
(1526)
(5.718)
(119.5325.5)
(3975)
(51.358.8)
(98100)
(76.393.7)
(7.117.29)
(7.17.24)
(6.727.1)
(3851.5)
(2744.5)
(7.518.1)
(15.919.8)
(-13.5 to -7.5)
(2.47.9)
(3.13.8)

(110.3140.5)
(60101.3)
(5.28)
(2.84.8)
(1,0681,980)
(22.541.2)
(490880)
(400668)
(305526)
(1323)
(7.116.2)
(147337)
(40.571.5)
(5261)
(98.1100)
(6087.8)
(7.137.33)
(7.037.24)
(6.747.14)
(3852)
(24.538.5)
(7.116.7)
(17.421.6)
(-11.7 to -5.3)
(1.66.8)
(2.83.6)

SVI stroke volume index, ITBI intrathoracic total blood index,

GEDVI global end-diastolic volume index, ELWI extravascular
lung water index, SVV systolic volume variation, a arterial, pHi
gastric intramucosal pH, EtCO2 end-tidal CO2

152

Metabolic parameters

Discussion

Arterial and venous pH progressively increased while pHi

did not change from very low values. Lactic acid and K?
decreased, while arterial HCO3 and BE did not change.
The comparison of ROSC between the four therapeutics groups has been previously published [13]. No
differences were observed between groups when parameters were compared (data not shown).
CI, MAP, and SVRI were similar in the animals who
received vasoconstrictive drugs (adrenaline and terlipressin)
and those who achieved ROSC with chest compressions and
ventilation only.
Table 4 shows the comparison between the status
before arrest and 30 min after ROSC. CI and SVI,
although in the normal range, were significantly lower
after ROSC. Volume status parameters, ITBI and GEDVI,
were also lower than baseline, while ELWI achieved
baseline values.
Venous, cerebral, and tissue hemoglobin oxygen saturation were slightly lower than baseline after ROSC.
Arterial and venous pH and HCO3 were lower than
baseline, while BE and lactic acid were significantly
higher. Gastric tonometry showed significantly lower pHi
values 30 min after ROSC than prior to arrest.

Our study is the first that has analyzed the changes of

hemodynamic, respiratory, and tissue oxygenation and
perfusion parameters during and after a resuscitated
asphyxial CA in an infant animal model.
Cardiovascular parameters
Immediately after the asphyxial event a sudden hypercapnia and hypoxia occurred, accompanied by a transient
tachycardia with arterial hypertension and increase in
systemic vascular resistances. However, 5 min later,
progressive bradycardia and hypotension developed, with
low CI, pulmonary hypertension, tissue hypoxia, and
lactic acidosis, that worsened until CA was confirmed and
CPR started. Similarly, in CA due to induced ventricular
fibrillation (VF), Engoren et al. [14] found at 5 min a 46%
decrease of cardiac output, accompanied by metabolic
acidosis, venous hypoxemia, and hyperkalemia.
We observed that during CPR, MAP, CI, and EtCO2
decreased progressively, with worsening of lactic acidosis.
This suggested that in this model of asphyxial CA,
standard CPR performed following current guidelines

Table 4 Comparison of parameters: pre-arrest versus post-resuscitation (n = 26)

Parameter

Basal (initial)

30 min after ROSC

HR (beats per min)

MAP (mmHg)
CVP (mmHg)
CI (l/min/m2)
SVRI (dyn 9 cm5/m2)
SVI (ml/m2)
DPmax (mmHg/s)
ITBI (ml/m2)
GEDVI (ml/m2)
ELWI (ml/m2)
SVV (%)
Cerebral saturation (%)
Renal saturation (%)
Arterial saturation (%)
Venous saturation (%)
Arterial pH
Venous pH
pHi
PaO2 (mmHg)
PaCO2 (mmHg)
EtCO2 (mmHg)
Gastric PCO2 (mmHg)
Arterial HCO3 (mmol/l)
Arterial BE
Lactic acid (mmol/l)
K? (mmol/l)

116
90
8
4.83
1,425
40.4
910
618
463
16.5
12.9
58.5
61
100
81
7.4
7.35
7.21
180
40
35.5
9.3
26.5
1.1
0.8
3.8

123.5
87
6.5
4
1,592
32.4
690
521
395
16
12.5
53
55
99.9
73
7.26
7.21
6.96
197
42
27
9.9
20.2
-7.7
3.8
3.2

0.044
0.251
0.417
0.007
0.845
0.011
0.948
0.009
0.009
0.938
0.233
0.858
0.232
0.060
0.191
\0.001
\0.001
0.004
0.231
0.133
0.271
0.062
\0.001
\0.001
0.002
\0.001

(101.5135.5)
(76.5101.5)
(610)
(4.05.7)
(1,1051,740)
(3446)
(7101,295)
(479762)
(361607)
(1325)
(9.817.3)
(51.365.8)
(5763)
(99100)
(6889.3)
(7.347.46)
(7.297.4)
(7.157.3)
(120211.5)
(34.445)
(31.840)
(6.510.8)
(22.129.7)
(-3.74.6)
(0.51.1)
(3.34.1)

Cerebral and renal oxygenation were monitored by near-infrared

spectroscopy (NIRS)
HR heart rate, MAP mean arterial pressure, CVP central venous
pressure, MAPP mean arterial pulmonary pressure, CI cardiac
index, SVRI systemic vascular resistance index, SVI stroke volume

(110.3140.5)
(60101.3)
(5.28)
(2.84.8)
(1,0681,980)
(22.541.2)
(490880)
(400668)
(305526)
(1323)
(7.116.2)
(40.571.5)
(5261)
(98.1100)
(6087.8)
(7.137.33)
(7.037.24)
(6.747.14)
(147337)
(3852)
(24.538.5)
(7.116.7)
(17.622.4)
(-11.7 to -5.3)
(1.66.7)
(2.83.6)

index, ITBI intrathoracic total blood index, GEDVI global enddiastolic volume index, ELWI extravascular lung water index, SVV
systolic volume variation, a arterial, pHi gastric intramucosal pH,
EtCO2 end-tidal CO2

153

achieves only a low cardiac output and perfusion state.

Consequently, new CPR methods that might offer better
immediate effects on hemodynamic, respiratory, and tissue oxygenation/perfusion parameters should be explored.
After ROSC, a rapid restoration of hemodynamic
parameters occurred. Heart rate and CI significantly
increased and then decreased progressively, while MAP
and SVRI had a slight increase and later decrease; DPmax
progressively decreased, while systemic vascular resistances did not change significantly. These data could
indicate, at least in our model of asphyxial CA, that in the
immediate period after ROSC, although MAP and CI
restore, an impairment of myocardial contractility exists
[15]. Furthermore, it is remarkable that systemic vascular
resistances did not increase despite some animals receiving
vasoconstrictors (adrenaline and terlipressin) during CPR.
Our results indicate that additional studies assessing
the short- and long-term evolution of these parameters as
well as the effectiveness of drugs that could improve
myocardial contractility in this period are needed [15, 16].
Femoral arterial thermodilution measurement has been
used in infantile animal models and in children [1724]; it
has showed an acceptable correlation with pulmonary
arterial thermodilution by using a Swan-Ganz catheter
[19, 23], and therefore it might be a reliable and less
invasive hemodynamic monitoring tool in the post-CA
period in children.
No prior studies have analyzed the evolution of CI and
volume status in children or infantile animal models of
CA. In our investigation, ITBI and GEDVI slightly
increased after ROSC, but they did not reach the prearrest values.
Several studies had indicated that after ROSC there is a
sepsis-like syndrome with relative decrease of intravascular volume [2527]. Our results support those findings
and suggest that some fluid challenge could be needed
after ROSC, even in the case of hypoxic CA and despite
normal CI, MAP, and SVV data. This treatment could
contribute to improve general hemodynamics and tissue
perfusion [2527], although its potential risk of increasing
right ventricular distension must be also considered and
should be guided by a strict monitoring of volume status.
On the other hand, ELWI, which was very high just
after ROSC, rapidly and progressively decreased to prearrest values at 30 min. This result could point to the
development of pulmonary interstitial edema during CA
and CPR that rapidly resolved after ROSC. In this sense,
ELWI could constitute an early marker to the presence of
pulmonary edema after ROSC and could help to monitor
its evolution with therapy.

improved after ROSC, although with values below baseline. Prior studies have assessed the potential usefulness of
brain NIRS for the control of brain perfusion-oxygenation
status in children during cardiac surgery and in animal
models of newborn asphyxia and CA [12, 2830], but no
studies have reported results of NIRS during cardiac arrest
and subsequent CPR. Our results indicate that brain saturation decreases during asphyxial CA, its values remain
low during CPR, and partially restore after ROSC, a profile
that suggests a persistence of tissue hypoxia after resuscitation that could contribute to brain damage and poor
neurological outcome.
Several studies have analyzed the correlation between
brain and renal NIRS and other parameters of systemic
and tissue perfusion. Chakravarti et al. [29] found that
cerebral and renal saturation measured by NIRS had a
good correlation with hyperlactacidemia in children after
cardiac surgery. Kaufman et al. [28] found that abdominal
site NIRS saturation exhibits a strong correlation with
gastric pHi, serum lactate, and SVO2 in infants following
cardiac surgery, suggesting that the NIRS is an adequate
non-invasive measurement of splanchnic SO2.
No previous studies on the potential utility of renal
NIRS in CA are available. In our experiment, both
cerebral and renal NIRS decreased during CA and
restored after ROSC. These results suggest that more
specific studies are needed in order to evaluate its
potential role to predict the CA outcome and its eventual
correlation with hemodynamic status and long-term
neurological outcome.
Respiratory and metabolic parameters

Blood gas analysis after ROSC showed a slowly progressive increase of arterial and venous pH, HCO3, and
BE, concomitant with an increase of brain and renal
saturation as well as a quick decrease of lactic acid and
K. However, pHi did not change during the 30 min after
ROSC, a fact that indicates the persistence of splanchnic
hypoperfusion after successful resuscitation. Although
pHi has been used to monitor splanchnic perfusion
during shock and cardiac surgery in children [3134], no
studies have assessed its potential utility to monitor the
restoration of splanchnic circulation after CPR. Our
results indicate that pHi remains very low at 30 min
after ROSC, despite normal global hemodynamic
parameters and improvement of other tissue perfusion
parameters like cerebral and renal saturation and lactic
acid. These facts suggest that a more aggressive therapeutic approach might be needed during the post-ROSC
period in order to promptly restore the splanchnic perPerfusion parameters
fusion and consequently to lessen the potential risk of
secondary multiorgan failure.
Brain and tissue saturation values decreased with aspOur study has several limitations. We only analyzed
hyxia, remained very low during CPR, and progressively the events that occurred during the first 30 min after

154

ROSC; therefore we cannot know how long these will

persist. Animals were treated with different drugs during
CPR; although no significant differences between the
studied parameters were found when the four therapeutic
groups were compared, a potential bias in the results due
to this circumstance cannot be excluded.
We conclude that after asphyxia, a sudden hypoxia and
hypercapnia occurs and progressive bradycardia and tissue
hypoxia follow. Standard CPR is not able to achieve an
adequate tissue perfusion and oxygenation and, in consequence, progressive lactic acidosis arises. After ROSC and
despite a quick restoration of hemodynamic, respiratory,

and global metabolic parameters, signs of tissue and

especially splanchnic hypoxia persist. Our data may serve
as a reference for further studies that analyze the effects of
new CPR methods on tissue perfusion and oxygenation
during CPR and after ROSC.
Acknowledgments This study was partially supported by a
research grant from the Spanish Health Institute Carlos iii PI05/
0807 and the grant N. RD08/0072: Maternal, Child Health and
Development Network) within the framework of the VI National
I?D?i Research Program (2008-2011).

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