Cardiorespiratory and conjunctival oxygen tension monitoring during crystalloid resuscitation after hemorrhage

Cardiorespiratory and Conjunctival Oxygen Tension Monitoring During Crystalloid Resuscitation After Hemorrhage Edward

Abraham

and Stan Fink

Conjunctival oxygen tension (PcjO,) monitoring provides a continuous, noninvasive assessment of tissue oxygenation and perfusion. In this study. the relationship between PcjO, and standard cardiorespiratory variables was examined during sequential, stepwise crystalloid resuscitation after acute hemorrhage to a mean arterial pressure (MAP) of. 40 mm Hg. Posthemorrhage values for PcjO, were approximately 5% of prehemorrhage values. Blood pressure rose rapidly during the early stages of resuscitation, and after 40% of the shed blood volume had been replaced with crystalloid was no longer significantly different from prehemorrhage values. PcjO, rose in a

linear manner during resuscitation and achieved values that were not significantly different from control when 70% of the shed blood volume had been replaced with crystalloid. When all of the shed blood volume had been replaced with crystalloid, cardiac index, left and right cardiac work index, and oxygen delivery remained significantly less than control levels. These results indicate that PcjO, normalizes before crystalloid resuscitation is complete, but after blood pressure and other noninvasively measured parameters return to prehemmorrhage levels. Q 1987 by Grune & Stretton, Inc.

RYSTALLOIDS are usually the first intraC venous fluids administered to patients with blood loss in both prehospital and emergency

put, and increased tissue metabolism that may result in cellular ischemia secondary to diminished tissue perfusion and oxygenation. Because regional variations in perfusion exist during hemorrhage and resuscitation,4V5 the degree of impairment in tissue oxygenation is not the same in all anatomic sites. While invasive hemodynamic monitoring permits determination of oxygen delivery and consumption for the whole organism, assessment of the adequacy of oxygenation in specific anatomic sites was difficult before the development of miniaturized oxygen electrodes that can be put directly on these actively metabolizing tissues. Placement of a miniaturized polarographic oxygen electrode against the palpebral conjunctival surface permits continuous, noninvasive monitoring of tissue oxygenation at this peripheral site.6 Because the conjunctiva is not keratinized, the unheated electrode accurately measures oxygen tension in the area that lies directly beneath the sensor.’ Stabilization of the conjunctival sensor is rapid in clinical situations, and meaningful, steady state values are available within 60 seconds of insertion.8 In patients with normal cardiac output and peripheral perfusion, conjunctival oxygen tension (PcjO’) reflects Pa02.9 However, in pathophysiologic states where peripheral perfusion and oxygen delivery are reduced, PcjO, becomes disassociated from PaO,. For example, decreased cardiac output, resulting from myocardial infarction or diminished preload associated with hemorrhagic hypovolemia, reduces tissue oxygen

deparfment situations. Several studies have demonstrated the ability of crystalloids to significantly improve hemodynamic and oxygen transport variables after hemorrhage.lV2 Because crystalloids rapidly equilibrate with the interstitial and intracellular spaces, large volumes of these agents often are required to maintain intravascular volume, cardiac output, and oxygen delivery. Noninvasive assessment of the adequacy of crystalloid resuscitation may be difficult, since the variables that can be followed, such as blood pressure and heart rate, correlate poorly with intravascular volume. In particular, vital signs are often normal early in resuscitation before intravascular volume and cardiac output have been fully restored.3 A major function of the combined cardiorespiratory systems is maintaining tissue oxygen at levels that permit efficient aerobic cellular metabolism. Pathophysiologic conditions such as hemorrhage are associated with reduction in arterial oxygen content, decreased cardiac out-

From

the Department

of Medicine,

UCLA

Medical

Cen-

ter. Address reprint requests to Edward Abraham, MD, Division of Pulmonary and Ciritical Care Medicine, Department of Medicine, UCLA Medical Center, Los Angeles, CA 90024. 0 1987 by Grune & Stratton, Inc. 0883-9441/87/0204-0003$05.00/O

256

Journal

of Critical

Care, Vol 2, No 4 (December),

1987:

pp 256-263

CARDIORESPIRATORY

AND PcjO,

MONITORING

delivery and Pcj02, even though PaO, may remain normal.” Peripheral vasoconstriction associated with these low flow states”~‘* accentuates the decrease in tissue oxygenation and results in a larger disparity between Pcj02 and PaO, values than would be predicted from the decrease in oxygen delivery alone. Large, clinically significant decreases in PcjO, and Pcj02/Pa02 occur during the early stages of hemorrhage and precede any change in vital signs. In normotensive patients with a history of bleeding, a PcjO,/PaO, ratio less than 0.5 was associated with loss of more than 15% of blood vo1ume.i3 During gradual hemorrhage in dogs, PcjO, fell significantly and PcjO,/PaO, achieved values less than 0.5 after 18% of the blood volume had been removed.3 The decrease in Pcj02 preceded any change in other noninvasively measured parameters, such as blood pressure, and occurred concomitantly with the initial decrease in cardiac output and oxygen delivery. When blood products are used during resuscitation from hemorrhage, PcjO, appears to be one of the last physiologic variables to return to normal values. In dogs a staged resuscitation utilizing the blood removed during hemorrhage found that PcjO, returned to baseline values only after 90% of the blood volume had been restored.14 Several case studies have monitored PcjO, during fluid resuscitation after trauma and hemorrhage.‘4,‘5 In these cases, the PcjO,/ PaO, ratio reached values greater than 0.5 after blood pressure had normalized, and achievement of this level of PcjO,/PaO, appeared to correlate with restoration of intravascular blood volume. Although clinical case studies” suggest that PcjO, and Pcj02/Pa02 rise to normal levels during crystalloid resuscitation after hemorrhage, the changes in cardiorespiratory variables and intravascular volume that accompany this normalization of PcjO, have not been determined. It may be clinically important to know when in resuscitation Pcj02 achieves normal values. If PcjO, normalizes before blood volume is restored, additional fluids should be administered after this point. If PcjO, reaches normal values after blood volume is restored, resuscitation should be stopped before these values are attained. The present study was designed to explore the relationship between PcjO, and cardiorespiratory and blood volume values during

257

staged crystalloid rhage.

resuscitation

MATERIALS

Experimental

AND

after

hemor-

METHODS

Animals

Eight mongrel dogs, weighing 17 to 22 kg (mean 18.9 + 0.7 (SEM) kg) were used for this experiment. The experimental protocol was approved by the UCLA Animal Research Committee and met NIH guidelines for animal use. The dogs were anesthetized with pentobarbital sodium intravenously in loading doses of 30 to 40 mg/kg. Maintenance doses were given as required. All animals were intubated with a cuffed 8 French endotracheal tube and ventilated with a pressure-cycled respirator (Bird Technology, Palm Springs, CA). Peak inspiratory pressures were kept below 30 mm Hg. Ventilation was maintained with 70% oxygen administration.

Conjunctival

Oxygen Sensor

The conjunctival oxygen sensor (Biomedical Sensors Inc, Kansas City, MO) consists of a miniaturized polarographic oxygen electrode and solid-state thermistor mounted on a polymethylmethacrylate conformer. On insertion the oxygen electrode and thermistor rest gently against the lateral superior palpebral conjunctiva. After preparation of the electrode, a two-point calibration to zero solution (PO, 0 torr) and to room air (pOZ 157 torr), was performed. The sensor then was inserted into the right eye of the dog and allowed to stabilize. Stabilization of conjunctival measurements was considered to be achieved when three consecutive readings, taken 60 seconds apart, differed by no more than 5%. In all animals, stabilization occurred within ten minutes after insertion of the conjunctival sensor.

Experimental

Protocol

After each dog was anesthetized with pentobarbital, intubated, and the conjunctival sensor had stabilized in situ, the femoral artery and vein were exposed bilaterally. A no. 7 French balloon-tipped flow-directed thermodilution catheter was passed into the pulmonary artery through the right femoral vein. Bilateral femoral artery catheters were inserted. The pulmonary artery and femoral artery catheters were continuously Rushed at 3 mL/h with 5% dextrose solution containing 1 U/mL heparin. Statham P23db pressure transducers (Gould Electronics, Oxnard CA) and a Grass Model 7 4-channel recorder (Grass Instruments, Braintree, MA) were used to monitor femoral artery, pulmonary artery, right atrial, and pulmonary capillary wedge pressures. The transducers were set to the midthoracic level of the dogs and were calibrated against a mercury sphygmomanometer. The dogs were given heparin (100 U/kg) intravenously. Data sets included measurement of PcjO,, conjunctival temperature (Tcj), and arterial and mixed venous PO,, PCO*, and PH. Arterial and mixed venous blood samples were anaerobically withdrawn into heparinized 1 mL syringes and immediately analyzed with a Corning Model

258

ABRAHAM

been replaced by Ringer’s lactate. A scintillation counter measured plasma radioactivity in duplicate, together with a standard dilution of the injectate. Counting was carried out for at least ten minutes, or until there was less than 1% counting error.

178 blood gas machine. At the same time, systemic arterial, right atrial, pulmonary artery, and pulmonary capillary wedge pressures were recorded. Cardiac output was measured using injection of 10 mL of a 5% solution of dextrose in water at 0°C through the proximal port of the pulmonary artery catheter with integration of results by a cardiac output computer (Santa Barbarq Medical Instruments, Santa Barbara, CA). Derived cardiorespiratory variables were calculated by standard formulae. The cardiorespiratory variables utilized in this study and their abbreviations are shown in Table 1. After a 45-minute control period in which three complete data sets were collected at 15-minute intervals, the animal was allowed to bleed from the femoral artery catheter into a reservoir until the mean arterial pressure (MAP) was 40 mm Hg. The blood pressure was maintained at 40 mm Hg for 30 minutes by withdrawing or infusing blood as required. Data sets were taken every 15 minutes during this period. After 30 minutes at a MAP of 40 mg Hg, Ringer’s lactate was given to the animal intravenously at the rate of 100 mL every 10 minutes. Data sets were collected five minutes after each crystalloid infusion, immediately prior to the next intravenous fluid administration. After all of the shed blood volume had been replaced by crystalloid, the dog was killed with a massive overdose of pentobarbital. Plasma volumes were determined by the radioisotope dilution technique, using I ‘*‘-labeled human serum albumin (RIHSA).‘69’7 Ten microcuries of RIHSA were injected IV, and postinjection blood samples were drawn 10 and 20 minutes later. Blood samples were also drawn after hemorrhage was completed, when PcjOl measurements returned to prehemorrhage levels and when all the shed blood volume had Table

CaO, cvo, C(a-40, Cl co CVP DO, HR LCWI

Arterial

oxygen

Mixed venous Arterial-mixed Cardiac index Cardiac

content oxygen

Tcj vo* WP

Variables Fwmulae for Derived Variables -

content

output

Left cardiac

work

10

Cl x MAP x 0.0144 -

pressure (CaO, pressure pressure

Arterial oxygen saturation Stroke index Systemic vascular resistance

wedge

- CvOJCaO, -

index

index

Pulmonary artery blood temperature Conjunctival temperature Oxygen consumption capillary

CaO, - CvO, CO/surface area -

Conjunctival oxygen tension Pulmonary vascular resistance Right cardiac work index

Pulmonary

difference

CaO,xClx

index

Oxygen extraction ratio Pulmonary artery systolic Pulmonary artery distolic

SVRI Tcore

The cardiorespiratory and conjunctival variables that accompanied hemorrhage and resuscitation were presented in Table 2. The initial, prehemorrhage plasma volume was 1,334 + 116 mL. The amount of blood removed during the initial hemorrhage, and replaced with Ringer’s lactate during the resuscitation stage averaged 49.7 f 2.9 mL/kg.

Central venous pressure Oxygen delivery Heart rate

0,Ext PAS

RCWI SaO, SI

RESULTS

content oxygen venous

Mean arterial pressure Mean pulmonary arterial

PcjO, PVRI

Measured and derived variables were grouped and meaned for the control, posthemorrhage, and resuscitation stages. The resuscitation period was further divided into ten stages, each corresponding to return of 10% of the shed blood volume with crystalloid. Cardiorespiratory parameters were analyzed for each of these resuscitation increments. All variables are expressed as mean + SEM. Comparison of cardiorespiratory and conjunctival values to the control group was performed using one way ANOVA and Dunnett’s test. Regression analysis and calculation of correlation coefficients was performed using the least squares method. A P value greater than .05 was not considered significant.

Variable

MAP MPAP

PAD

Data Analysis

1. Cardiorespiratory

Abbreviations

AND FINK

pressure

79.92 LMPAP - WP)/CI Cl x MPAP x 0.0144 79.96

CI/HR (MAP - CVPNI -

C(A-v)O,

x Cl x 10 -

bxr)

“amble

(mm

Imm

PAS

PAD

(mm

Hg)

Idyll

Ig/MI

(g/Ml

LCWI

RCWI

1%)

,%I

,CI

283 + 32 0.76 + 0.07 157 + 11 142 _f 4 3+1 19 * 3 11 + 1 14 + 1 551 4.17 * 0.53 26.3 i 1.7 2827 r 231 175 t 27 8.7 t 1.3 0.82 + 0.11 9* 1 371 t 15 34 + 4 7.40 i 0.04 19.7 + 2.0 99.8 80 t 5 41 + 4 7.35 + 0.04 21.8 + 1.5 87.5 t 1.9 18.9 r 1 9 16.3 + 1.8 2.5 + 0.3 806 f 157 105 + I8 14 + 2 38.7 i_ 3.6 37.7 k 0.5 35 2 $ 0.5

Prehemarhage

l P c .05 v prehemorrhage tP < .Ol v prehemorrhage

TCl (Cl

T core

Hct

O2 Ext 1%)

knL/rnl”lM’)

vo,

O2 fmL/dLl

Cb-4

(mL/mmlM21

(mL/bl

DO,

(mL/dLl

CvQ,

,%I

02 Satv

Ca02

lmEq/Ll

korr)

HCO,”

PHV

PVCO,

Itar)

o* Sata

PVQ,

(mEq/L)

(tar)

kxrl

HC03a

PHa

PaCO*

Pa02

RR (breathdmml

S/Cdl

(dyn s/cm51

PVRl

Hg)

Hgl

Hgl

SVRI

SI (mL/M’)

Hg)

Hgl

Cl (L/mm/M2)

WP

(mm

(mm

CVP

MPAP

(mm

MAP

HR (beats/mm)

PcPJPaoz

PC@,

2.

*

t

I,

o.o,+

- --.

value. value.

10%

t

1.3.

1.9t

0.9t

34.2

38.4

29.2

55

99 rot

0.7

2.0+

+ 0 5

f

i

t

+ 40

170 i 49+

f

f

5.1 8.1

1.4

+ 9.3t

t

14.2

44.9

19.7

* 0.03’

es*

51 7.20

+4t

99.8

i- 0.5.

k 0.03’

31

18.1

7.31

r 0.04t

7.3

1.29

1.

1.0t

389 5 73. 2.2 + o.fst 0.15 r 0.04t 9+1 370 + 22 33 * 4 7.34 * 0.04 17.0 r 1.1 99.8 34 + 2+ 47 t 8 7.25 * 0.04 19.9 + 1.5 53.9 f 5.1t 15.1 t 1.2’ 8.0 1 0.9t 72 + I.tt 187 t 33t 93 * 22 47 + 5t 30.9 t 2.2t 37.3 r 0.5 337+05. --.-

+ 972t

i

t 0.26t

2 +

2+_1 11 * 2t 5* It 8 * 2t

11029t

+ 0.051

2 2.

9*1

* 0.071

+ 0.8t

77

* 947t *

1.0

f

k Lot

1.ot

0.8

t

34.0

1.8t

IO 7

t

+ 4t

+ 29

t 56t

37.2

258

37

107

285

4.7 + 0.6t

7.9

12.6

+ 4 St

63.8

1.3

t

t 0.04

f 8

+ 3t

99.8

t

+ 0.05

*4

20.4

7.29

44

38

17.6

7.38

31

376 k 25

0.29

3.8

289

4730

+ 2.1t

13.4

1. + 0.36

2.22

2e

9 f 2.

7 + 2.

14

3*1

170 + 17 117 * lot

0.28

+ 15t

r

* 6

14.

t 0.11t

3+_1

12.1

2.41

I*

1.2t

+ 38

+ 583.

*

t 0.42t

1 *

lt

It

37 50 7.22 21.6 58.0 13.5 7.5 8.0 327 146 44 27.3 38.3 35.2

19.2

7.32

+ 0.05t

3

f i t i + t + + t + + t + t

99.8

+

,t 2’ 0.01‘ 0.7 1.2t 2.0t 0.9t 1.2t 7Ot 35 2t 3.6t 0.5 0.5

1.0

f 0.02

f

k 40

9+1

37

376

0.27

4.7 + 1.ot

252

5 + Se

Values

+ 43t

40%

13 + 2.

132

195

0.34

124

4575

30% 104

20% + ,rt

and Cardiorespiratory

Tension

172 i 16

0.13

43

7704

Oxygen

I+ It 0.23t o.st 1221t 199. 0.3t o.o,t

rt

3t

327 + 30 32 * 2

9*1

7 k 1 + 1.18 + 5.6 f 8394 * 486 + 1.5 f 0.10 *

5+

11 *

332 1tt 0 11 e0.04t 205 * 1st s9* ?t 3*1

Conjunctival

37 + 2t 1 t_ 1. 82 I+ 5* 1t s+ t+ 2* 1. 0.98 + 0.15t 8.0 * o.,t 3206 + 329 362 + 101. 0.5 * 0.1 t 0 08 f 0.02t 9*1 340 + 22 28 t 3. 7.40 t 0.05 15.5 t 1.3’ 99.8 20 i 37 52 f 8‘ 7 23 t 0.04* 20.7 t 1.4 24.8 + 5.5t 18.9 i 1.0 4.8 t 1.3+ 14.2 + 1 3t 180 f 2s+ ,38 t 28 78 + 5t 39.0 + 1.9 37.5 f 0.5 33.5 r 0 4’

18,

0.04

14+4+

Po*th*marhage

Table

0.10.

0.29. 2.2. 329 36 0.6.

2. 1. 1.

30t 0.08t 12 7.

34.3

37.2

24.9

33

123

370

4.1

8.2

12.3

68.6

19.9

7.29

42

39

18.1

1.0

l.Ot

32+

1.7t

? 0.5

r 0.8

f

* 3t

+ 15

*

+ 0.5t

I 0.7t

i

2 2.5t

+ 0.21

2 0.02

t 5

+ 2t

99.8

t

+ 0.08t

* 35t

60%

2.

1

+ 22 * 3 k 0.03 + 1.2 99.8 42 + 2t 46 2 3 7.29 + 0.02 22.2 e 0.8 59.9 i 2.7t 12.4 f t.lt 8.4 t 0.8t 4.0 f 0.5t 331 + 28t 109 + 18 31 t2t 24.8 t_ ?.8t 37.4 t 0.8 34.6 i 0 7

379 36 7.36 21.9

9A

6e 1. Sk,* , + 1’ 2.74 t 0.2st 16.5 * 1.8. 3909 + 323. 202 + 42 5.3 + 0.7. 0.31 -r O.D5t

13 *

70%

From

f

20

t 2.

7.30 22.1 72.7 11 5 8.3 3.3 346 102 29 23.4 37.2 34.4

45

44

19.2

7.36

Yk 1.3

+ 0.02

* 3

+ 35

t 0.08.

e 0.9.

+ 30

t 0.02 ? 1.0 i 3.5t i I.lf i I.,t + 0.4. f 41t t 19 f 3t ‘+ 2.0t t 0.8 f 0.8

+ 3

+ 2t

99.8

9*1

34

366

0.41

8.1

181

3*1 3.04 + 0.28’ 18.9 + 2.4. 3811 + 381.

10

135 i 9 2+, 14 * 3’ 7+ 1.

168

260 + 44 0.71 + 0.10

Resuscitation

170 + 1, 132 f 7 3+1

0.56

215

Crystalloid

368 * 26 32 2 4 7.37 +_0.04

9*1

172 + 0.47 t 172 + 125 f 3*1 13 + 7 + 9+ 3*1 3.08 + 18.4 e 3352 t 159 + 5.5 * 0.40 +

50%

During

* 59

80%

2+

+ 0.20.

1.

1’

1.

* 2.

+ 37

+ 4t

99.8

1.3

+ 3.9’ 1.0t

0.5t 0.7 38t 24 5t 1.5, 0.4 0.5

+

t + + t f i+ t

10.4 7.5 2.9 353 98 27 20.7 38.3 35.5

k 0.9 75.0

22.9

46 t 2 7.30 + 0.02

48

21.0~

394 t 45 36 + 2 7.37 * 0.02

9*1

7.0 * 0.3. 0.48 + 0.04.

182

18.7 + 2.2. 3357 + 283

3.41

lo?

7*

14

3*1

0.88 f 0.13 186 + 13. 144 * 5

269

Hemorrhage

90%

15

2+1

+ 7

*

+ 0.07

3t 2 0.02 0.8 3.3t 1.ot 0.9t 0.3.

5 1.8t

+ 3t

+ 20

r 5Dt

* + * * + + t f

99.8

37.4 t 0.7 34.5 + 0.7

22.4

30

44 48 7.31 23.4 72.8 11.2 7.9 3.3 385 115

377 e 32 35 * 4 7.35 t 0.02 21.6 t 1.0

9*1

k + + *

3273 183 8.9 0.43

245 38 0.8. 0.08.

* 2.0

+ 0.28.

t + 1.

21.2

3.41

9*1*

7 + 1’

14 t 2.

138

185

0.71

270 + 35

100%

f6

*

1.5.

* 0.09*

+ 0.6.

e 48

* 215.

*

* 0.19’

1.5

r

3.5, 0.8t 0.7t 0.4 28t 12 3t 1.3, 0.6 0.8

1.3

+ 0.03

*4

+ 3t

99.8

i

+ 0.05

72.1 * 10.8 + 7.5 t 3.2 * 323 + 98k 30 k 21.3 + 37.2 t 34.3 +

21.6

7.34

41

42

19.5

7.41

373 + 32 29 * 5

9tl

8.0 0.45

15

* 2= 3+2

182

3518

19.4

3.06

ID

8+2

15 I2

4-t,

136

163

269 I 24 0.72 * 0.03

260

ABRAHAM

Physiologic parameters reflecting conjunctival oxygenation and prefusion fell significantly with hemorrhage. Posthemorrhage values for PcjOz and PcjO,/PaO, were approximately 5% of control. Conjunctival temperature (Tcj) decreased 1.6“C from baseline. Hemorrhage also resulted in a marked decreased in systemic (MAP) and pulmonary artery systolic (PAS), diastolic (PAD), and mean (MPAP) pressures. Cardiac index (CI), stroke index (SI), left (LCWI) and right (RCWI) cardiac work induces, pulmonary (PVRI) and systemic (SVRI) vascular resistances, mixed venous oxygen tension (PvO,) and

AND

FINK

content (CvO,), and oxygen delivery (DO,) also were reduced. Significant increases in arterial to mixed venous oxygen content difference (C(av)O,) and oxygen extraction ratio (0,Ext) occurred posthemorrhage and were of sufficient magnitude to maintain oxygen consumption (VO,) at levels that were slightly, but not significantly, greater than baseline. PcjOz and Pcj02/PaOz rose in a linear manner during resuscitation. Both of these parameters achieved values that were not significantly different from control when 70% of the shed blood volume had been replaced with Ringer’s Lactate. 400

400

r

r= 0.81 300 k f ; 200 ‘3 CL

1 T

100 r = 0.96 8

A o+ 0

**

I 50

B

I 150

100

“0

4oc

400

3oc

300

k ,o ,N 2oc ‘C a

250

2

I 5 1

t 5 -s a

1oc

s Ml

1

I 4

Cardiac index ( L/min/M2

Mean Arierial Pressure 1 mm Hg )

III1 I- d-+ c @o

I 3

n

I

I

1

500

750

1000

Fig 1. Relationship between Pcj02 and MAP, from the eight dogs were combined for each stage SEM. Correlation coefficients (r) were statistically

M’ )

i

r= -0.87 +

100

r = 0.68

Oxygen Delivery ( ml/min/

200

+

25

50

75

Oxygen Extraction (% )

Cl. DO2 and 0, Ext during hemorrhage of the hemorrhage and resuscitation significant (P i .05) in each case.

and crystalloid resuscitation. Data protocol and are displayed as mean t

CARDIORESPIRATORY

AND PcjO,

MONITORING

261

At this point, the measured plasma volume was 2,279 + 208 mL, approximately 82% greater than control values. Significant correlations were present between PcjO, and cardiorespiratory variables during the crystalloid resuscitation (Fig 1). PcjOZ and CI were closely correlated, with r = .96 (P < .OOl). Slightly less strong, but highly significant association (P < .Ol) was found between PcjOZ and O,Ext, r = -.87, and PcjO, and MAP, r = 81. PcjO, and DO2 also were significantly correlated, r = .68 (P < .05). Blood pressure rose rapidly during the early stages of resuscitation (Fig 2). After 40% of the shed blood volume had been replaced with crystalloid, MAP had increased 95 mm Hg from the low levels present immediately posthemorrhage and was no longer significantly different from prehemorrhage values. The normalization of MAP with crystalloid infusion was accomplished primarily by maintaining significant elevated peripheral vascular resistance at all stages of the resuscitation. Cardiac output and hemodynamic variables related to cardiac output, such as SI, LCWI, and RCWI, remained significantly

I

20

,

1

.

I

40 60 80 Resuscitation (% 1

.

,

100

Fig 2. Relative change in PcjOz and MAP during crystalloid resuscitation after hemorrhage. MAP rises rapidly during the early stages of resuscitation, and does not differ significantly from prehemorrhage values when 40% of the shed blood volume has been replaced by crystalloid. In contrast, PcjO, remains significantly less than control values until the resuscitation is 70% complete. In all eight animals. normalization of MAP was achieved before PcjO, returned to control values.

below prehemorrhage levels throughout resuscitation. The hematocrit fell early in resuscitation and then continued to decrease as more crystalloids were given. At the end of the protocol, when the total volume of infused crystalloids equaled the amount of shed blood, hematocrit was only 60% of the prehemorrhage levels. CaO,, which is dependent on the hemoglobin concentration, also showed significant decrease during the crystalloid resuscitation, falling almost 43%. Most oxygen metabolism variables remained significantly less than prehemorrhage levels throughout resuscitation. DO*, which is dependent on both CaO, and CI, fell 78% immediately posthemorrhage, and remained 60% below the prehemorrhage value even after all of the shed blood volume was replaced with crystalloid. PvOz was significantly diminished throughout resuscitation. CvOl remained less than 50% of baseline values at all stages of the crystalloid resuscitation, reflecting the marked reductions in hematocrit and PvO,. Values for VOZ remained relatively stable during hemorrhage or resuscitation. The maintenance of VO, was largely due to large increases in C(a-v)O, and 0,Ext at all stages of fluid administration despite presistently low CI and DOZ. Even after the total shed blood volume had been replaced by crystalloid, C(a-v)Oz was 28% greater than baseline and 0,Ext was more than twice prehemorrhage levels. Measured plasma volume almost doubled during the crystalloid resuscitation. The initial, prehemorrhage plasma value of 1,334 + 116 mL increased to 2,402 + 164 mL after all of the shed blood volume had been replaced by Ringer’s lactate. The expansion of plasma volume during resuscitation (1,008 t 75 mL) was slightly greater than the average amount of fluid administered (948 + 85 mL) indicating that translocation of extravascular fluid into the intravascular space occurred during the resuscitation period. DISCUSSION

Abnormalities in oxygen transport and cellular oxygen utilization are early physiologic abnormalities in hemorrhage.‘8s’9 Decreaess in DO* associated with compensatory increases in 0,Ext to maintain VO, are the first cardiorespi-

262

ratory changes noted in hemorrhage,3 occurring after the loss of approximately 18% of blood volume. Decreases in hemodynamic parameters measuring systemic and pulmonary arterial pressures, such as MAP, MPAP, CVP and WP, occur after greater amounts of blood are lost. Tissue oxygenation has been measured in several anatomic sites during hemorrhage and resuscitation. Invasive placement of oxygen probes into myocardium,” muscle,20 kidney,21 and subcutaneous tissue22 demonstrated that tissue oxygen tension falls in each of these sites early in hemorrhage at the point when systemic oxygen delivery first becomes significantly decreased from normal, prehemorrhage levels. Similarly, noninvasive measurement of transcutaneous23 and conjunctival3 oxygen tension demonstrated a decrease in both of these variables in the early stages of hemorrhage before any changes in standard noninvasive parameters, such as heart rate and blood pressure, became apparent. PcjO, and Pcj02/Pa02 ratio were among the first set of physiologic variables to become significantly altered during hemorrhage and accompanied the initial changes in CI, SI, and 0,Ext. Several studies have examined the patterns of change in tissue oxygenation during reinfusion of shed blood after hemorrhage. In general, restoration of tissue oxygen tension to control, prehemorrhage values did not occur until resuscitation was almost complete. Tremper et a123 followed transcutaneous oxygen tension during the infusion period after hemorrhagic shock and found that prehemorrhage values were not achieved until more than 80% of the shed blood had been returned. In a previous study,r4 we measured PcjO, and cardiorespiratory variables during a stepwise resuscitation from hemorrhage and found that PcjO, did not return to prehemorrhage levels until more than 90% of the shed blood had been returned. Despite the widespread use of crystalloid solutions in the initial therapy of hemorrhage, no previous study has examined the relationship between noninvasive measures of tissue oxygenation and cardiorespiratory patterns during crystalloid resuscitation. In the present study, both blood pressure and peripheral tissue oxygenation (PcjO,) returned to prehemorrhage levels before all the shed blood volume had been replaced by

ABRAHAM

AND FINK

crystalloid. Despite this normalization of MAP and Pcj02, most other cardiorespiratory parameters remained significantly different from baseline, indicating that the resuscitation was incomplete. In particular, although VO, was maintained throughout the hemorrhage and resuscitation periods, DO2 was never more than 50% of prehemorrhage levels and 0,Ext was always more than twice control values. The early return of blood pressure to prehemorrhage values resulted primarily from intense peripheral vasoconstriction that compensated for the marked reduction in cardiac output. When MAP first returned to prehemorrhage levels, after 40% resuscitation, SVRI was approximately 62% greater than control levels. In constrast, the reasons for normalization of PcjO, during the crystalloid resuscitation are less clear. Pcj02 rose to prehemorrhage levels after 70% of the shed blood volume had been replaced with crystalloid. At this point, DOI had risen from the posthemorrhage value of 180 mL/min/M2 to 346 mL/min/M’, but still was reduced 57% below the prehemorrhage level. Several factors may contribute to the preservation of conjunctival oxygenation despite the reduction in total body oxygen delivery. Under normal conditions, conjunctival oxygen requirements must be substantially less than oxygen delivery to permit diffusion of oxygen to the avascular cornea. The situation in which tissue perfusion and oxygen delivery are in excess of cellular needs has also bee demonstrated to exist in subcutaneous tissue,24 and implies that cellular metabolic requirements in these anatomic locales can be met at levels of oxygen transport that are reduced substantially below normal. The fall in hematocrit that occurred during the cyrstalloid resuscitation resulted in diminished CaO, and DO2. However, the decrease in hematocrit from the prehemorrhage value of 38.7% to 23.4% after 70% resuscitation also produces a reduction in blood viscosity of approximately 36%.25 This change in blood rheology results in improved capillary flow that may partially compensate at the tissue level for the decrease in whole body oxygen transport. Regional variations in perfusion may favor the conjunctiva during resuscitation. The blood supply to the palpebral conjunctiva is derived from the internal carotid artery,26 and perfusion

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to this area may share characteristics with that of the brain, which utilizes the same blood supply. Cerebral blood flow and oxygenation are maintained even in low flow states’; a similar autoregulatory process in the conjunctiva would restore tissue oxygenation and PcjO, at an earlier point in resuscitation than that for other vascular beds and for the body as a whole. In this study, which utilized crystalloid resuscitation after hemorrhage, and in our previous

study,14 where blood was used, PcjO, and PcjO,/ PaO, returned to control, prehemorrhage levels before resuscitation was complete. In both studies blood pressure normalized even earlier than PcjOl, demonstrating the hazards in using MAP as an indicator of the adequacy of resuscitation. These results may be clinically significant since they suggest that blood and crystalloid resuscitation should be continued after conjunctival oxygenation is restored.

REFERENCES

1. Nees JE, Hauser CJ, Shippy C, et al: Comparison of cardiorespiratory effects of crystalline hemoglobin, whole blood, albumin, and Ringer’s lactate in the resuscitation of hemorrhagic shock in dogs. Surgery 83:639-647, 1978 2. Monafo WW: Volume replacement in hemorrhage, shock, and burns. Adv Shock Res 3:47-56, 1980 3. Smith M, Abraham E: Conjunctival oxygen tension monitoring during hemorrhage. J Trauma 26:217-224, 1986 4. Slater GI, Vladeck BC, Bassin R, et al: Sequential changes in distribution of cardiac output in hemorrhage shock. Surgery 73:714-722, 1973 5. Hirasawa H, Odaka M, Tabata Y, et al: Tissue blood flow in brain, liver, renal cortex, and renal medulla in experimental hemorrhagic shock. Crit Care Med 5141-145, 1977 6. Isenberg SJ, Shoemaker WC: The transconjunctival oxygen monitor. Am J Ophthalmol95:803-806, 1983 7. Fatt 1, Deutsch TA: The relation of conjunctival pO1 to capillary bed PO,. Crit Care Med 11:445-448, 1983 8. Abraham transcutaneous cardiopulmonary 1984

E, Smith M, Silver L: Conjunctival and oxygen monitoring during cardiac arrest and resuscitation. Crit Care Med 12:419-421,

9. Chapman KR, Liu FLW, Watson RM, et al: Conjunctival oxygen tension and its relationship to arterial oxygen tension. J Clin Monitoring 2:100-104, 1986 10. Abraham E, Smith M, Silver L: Continuous monitoring of critically ill patients with transcutaneous oxygen and carbon dioxide and conjunctival oxygen sensors. Ann Emerg Med 13:1021-1026, 1984 11. Bond RF, Manley ES, Green HD: Cutaneous and skeletal muscle vascular responses to hemorrhage and irreversible shock. Am J Physiol 212:4888497, 1967 12. Green HD, Rapela CE: Blood flow in passive vascular beds. Circ Res 1511 l-116, 1964 (suppl) 13. Abraham E, Oye RK, Smith M: Detection of blood volume deficits through conjunctival oxygen tension monitoring. Crit Care Med 12:93 l-934, 1984

14. Abraham E, Fink S: Cardiorespiratory and conjunctival oxygen tension monitoring during resuscitation from hemorrhage. Crit Care Med 14:1004-1009, 1986 15. Abraham E: Continuous conjunctival and transcutaneous oxygen tension monitoring during resuscitation in a patient. Resuscitation 12:207-211, 1984 16. Monson DO, Shoemaker WC: Sequence of hemodynamic events after various types of hemorrhage. Surgery 63~738-749, 1968 17. Shoemaker WC, Montgomery ES, Kaplan E, et al: Physiologic patterns in surviving and nonsurviving shock patients. Arch Surg 106:630-636, 1973 18. Littooy F, Fuchs R, Hunt TK, et al: Tissue oxygen as a real-time measure of oxygen transport. J Surg Res 20:321325, 1976 19. Niinikoski J: Tissue oxygenation in hypovolemic shock. Ann Clin Res 9:151-156, 1977 20. von der Kleij AJ, de Koning J, Beerthuizen G, et al: Early detection of hemorrhagic hypovolemia by muscle oxygen pressure assessment. Surgery 935 18-524, 1983 21. Nelimarkka 0, Halkola L, Niinikoski .I: Renal hypoxia and lactate metabolism in hemorrhagic shock in dogs. Crit Care Med 12:656-660, 1984 22. Matsen FA, Wyss CR, King RV, et al: Effects of acute hemorrhage on transcutaneous, subcutaneous, intramuscular, and arterial oxygen tensions. Pediatrics 65:881883,198O 23. Tremper KK, Waxman K, Shoemaker WC: Effects of hypoxia and shock on transcutaneous p0, values in dogs, Crit Care Med 7:526-531, 1979 24. Sugimoto H, Ohashi N, Sawada Y, et al: Effects of positive end-expiratory pressure on tissue gas tensions and oxygen transport. Crit Care Med 12:661-663, 1984 25. Castle WB, Jandle JH: Blood viscosity and blood volume: Opposing influences upon oxygen transport in polycythemia. Semin Hematol 3:193-198, 1966 26. van der Zee HT, Faithful1 NS, Kuypers MH, et al: On-line conjunctival oxygen tension as a guide to cerebral oxygenation. Anesth Analg 64:63-67, 1985