X-Message-Number: 2868
Date: 09 Jul 94 03:02:55 EDT
From: Mike Darwin <>
Subject: CRYONICS Case Report (2/3)

  -- Continued --

Agonal Course

	On 02-01-1994 the patient developed pulmonary edema (pink-
tinged frothy expectorate, gurgling breath sounds, loud rales 
bilaterally) accompanied by a decrease in oxygen saturation 
after receiving TPN.  TPN was discontinued at 22:30 under orders 
from Dr. McShane.  Oxygen was again started at 4LPM and the 
Standby Team was deployed.

	After the arrival of the Standby Team the patient's 
condition stabilized somewhat with apparent improvement of the 
pulmonary edema as evidenced by resolution of rales and 
improvement in oxygen saturatuion to 94-96% although the patient 
remained obtunded and febrile.  Oxygen administration was 

	Throughout the day on 02-02-1993 the patient continued to 
slowly deteriorate becoming unresponsive to all but painful 
stimuli (Glasgow Coma Score of 2) and exhibiting marked nuchal 
rigidity with flexor-extensor muscle rigidity.  The patient was 
placed on an eggcrate mattress and put on schedule of turning q. 
2 hrs. and basic care and comfort measures were continued     ( 
i.e., oral and perianal care and administration of pain 

	Beginning at 07:00 on 02-04-1994 until the time cardiac 
arrest occurred on 02-05-1994 the patient's pulse was in excess 
of 120 and other signs of shock, such as poor perfusion of  the 
lower extremities (mottling and coolness to touch), increased 
capillary refill time, and tachypnea were observed.   Vital 
signs are presented below in tabluar form beginning at 07:00 on 
02-04-1994 until the time of cardiac arrest. Vitals are also 
presented in graphic form at the end of this report.

Table III: Agonal Vital Signs

Time/Date   B.P.   CRF   H.R.   O2 Sat%     Resp.     Temp.  C               


07:00           N/A    3 sec.     148      82          40         
N/A         Glasgow Coma Score = 4

10:13           N/A    N/A       163      84          41         

03:30           N/A    N/A       141      68          24         

04:00           54/P    N/A      143      68          26          

05:00           56/P    N/A      147      61          32          
39 C       Resp. labored, irreg.

06:00           70/P    3-4       143      59          31          

07:15            48/P   >4        142      58          34          

07:45            48/P   >4        142      59          36          
N/A         Resp. increasingly shallow

08:40            48/P   >6        139      N/A       30          

09:15             N/A   2-3      123      91          34          
N/A         Turned to R side at 09:11

09:40             N/A   3-4      115      77          34          
35.5         Hands and feet cold/mottled

10:40             52/P   3-4      132      79          36         

13:09             N/A    N/A    129      81 .         21         

13:26             N/A    N/A    134     78            22        

13:50             N/A    N/A    134     88            17        

14:03              N/A   N/A    133     8              12        
N/A          Resp. very  shallow 

15:10             N/A    N/A    133     88            12        
38.5         Glasgow Coma Score = 2

15:20             34/P    N/A    136    87             13        
N/A         Turned to L side

15:32              0/P     N/A    0        35             0          
N/A          Resp./Cardiac arrest

	At 23:00 on 02-04-94 a blood sample was drawn from the 
patient's PICC line by the consulting physician and given to BPI 
personnel for subsequent analysis.  Analysis of the sample 
disclosed the following:

pH				7.378
pCO2				35.6
Na+				154 mM/L
K+				10.7 mM/L
Cl-				123 mM/L
Ca++				1.16 mM/L
Glucose 		  	               129 mM/L
Urea Nitrogen			72 mg/dl
Creatinine			1.6 mg/dl
Magnesium			2.4 mEq/L
Phosphorus			6.6 mg/dl
Protein, Total			7.1 g/dl
Albumin			3.5 g/dl
Globulin, Total			3.6 g/dl
A/G Ratio     			1.0
Bilirubin, Total                        	 0.4 mg/dl
Alkaline Phosphatase	               244 U/L
Lactate Dehydrogenase                    457 U/L
GGT				383 U/L
AST				66 U/L
ALT				43 U/L
Uric Acid			10.3 mg/dl
Iron, Total			20 mcg/dl
Iron Binding Capability		166 mcg/dl
Iron Saturation			12%
Triglycerides			215 mg/dl
Cholesterol, Total		160 mg/dl
Cholesterol, HDL		33 mg/dl
Cholesterol LDL (calculated)   	84 mg/dl
Cholesterol/HDL Ratio     		4.8
WBC				15.3 thous/mcl
RBC				3.4 mill/mcl
Hgb				11.3 g/dl
HCT				33.7  %
MCV				98 FL
MCH				32.9 PG
MCHC				33.7  %
RDW				14.8 %
Platelets				239 thous/mcl


	At approximately 15:00 the patient's respirations became 
extremely shallow and regular and the blood pressure became 
impossible to palpate.  The skin was diaphoretic and dusky to 
frankly cyanotic (lips, extremities) in appearance.  Pupils were 
dilated and only sluggishly responsive to light. Measurement of 
oxygen saturation either on the ear or finger was not possible 
due to "failure of signal acquisition"  presumably as a result 
of deep shock/failed tissue perfusion.   At that time Transport 
Team members quartered off-site were summoned and final 
preparation of transport medications was undertaken. 

	Cardiac and respiratory arrest occurred virtually 
simultaneously at 15:32 on 02-05-1994 and legal death was 
pronounced by the patient's consulting physician Ronit Katz, 

	Immediately following the pronouncement of legal death the 
patient was lifted from the hospital bed where cardiac arrest 
occurred and carried to the portable ice bath (PIB) which had 
been set-up in an adjacent room of the household.  External, 
closed chest cardiopulmonary resuscitation was begun using a 
Michigan Instruments Model 1004 Thumper cardiopulmonary 
resuscitator with ventilation by bag-valve-mask.  Time from 
cardiac arrest to the start of cardiopulmonary support was 2 
minutes.   A Darwin Esophageal Gastric Tube Airway (DEGTA) with 
integral copper-constantan thermocouple probe and balloon 
pressure monitor was rapidly placed to provide airway control 
and facilitate positive pressure ventilation.  Ventilation was 
then continued with the Thumper ventilator.  A Nellcor 
disposable end-tidal CO2 detetcor was interposed between the 
DEGTA and the nonrebreathing valve of the Thumper ventilator 

Figure 1: Darwin Esophageal Gastric Tube Airway

	Cardiopulmonary support  (CPS) was initiated at 15:34 at a 
rate of 80 compressions and 16 ventilations per minute 
(ventilation at a pressure of 30 cm of water and an FiO2 of 80%)  
Chest deflection was initially set at 2" and was then adjusted 
(compression force on chest) until the DEGTA balloon pressure 
read 100 mmHg on the dowstroke of the Thumper piston (to 2.5" 
sternal deflection). 

	 At approximately 15:45 the patient was carefully examined; 
the pupils were determined to be dilated and unresponsive to 
light and the skin color was pale with the lips remaining 
cyanotic.  Carotid pulse was barely palpable.

	External cooling commenced almost simultaneously with the 
start of  (CPS).  Cooling was initially by packing the patient 
in crushed ice in direct contact with the skin.  An array of 
tubing connected to three 10" in diameter plastic lawn sprinkler 
heads and connected to a Sears Model # 563-269500 submersible 
pump was placed such that one sprinkler head was at the 
patient's head, one on the thorax, and one on the abdomen.  The 
submersible pump was then used to pump the ice-cold water in the 
PIB over the patient to increase the rate of external cooling.

	Initial response to CPS was judged to be poor as indicated 
by initial end-tidal CO2 readings of 0.5%, continuation of 
pallor and cyanosis, and failure of the return of agonal gasping 
or pupillary responses.  This was confirmed by subsequent 
laboratory evaluation of a  blood sample drawn 81 minutes into 
cardiopulmonary support which showed a potassium of  12.0 mM and 
a glucose of  11.

	I.V. access was via the implanted PICC line using a 16 g 
Becton-Dickinson (BD) Interlink Syringe cannula.  Administration 
of transport medications began at 15:35 with I.V. push 
medications as follows:  epinephrine 12 mg at 15:35, nimodipine 
0.6 mg at 15:35, deferoxamine HCl 2 g at 15:38, sodium citrate 
7.2 g  at  15:40, Trolox 2.7 g at 15:43, sodium ascorbate 7.5 g 
at 15:50, 0.3 M tromethamine  in 500 cc of water for injection 
(THAM) infusion was begun at 16:05, sodium heparin 25,200 I.U. 
at 15:35, chloropromazine HCl 180 mg at 15:55, 
methylprednisolone HCl 1 g at 15:56, metubine iodide 4.2 mg at 
15:58, Cipro IV 400 mg at 15:56,  and gentamicin sulfate 60 mg 
at 16:03.  Maalox  250 cc, was given via the gastric tube of the 
DEGTA at 15:40.  

	Mannitol and Dextran-40 were omitted from initial transport 
medications due to the constraints of the low gauge BD Interlink 
cannula; by the time THAM infusion was completed preparations  
to connect the patient to the extracorporeal circuit were nearly 
complete and both of these medications were present in adequate 
concentrations in the priming fluid of the extracorporeal 
	The first esophageal temperature recorded from the probe 
(near the balloon) of  the DEGTA was 34.3 C at 15:39.  The first 
rectal temperature was 38.0 C and was obtained at 15:46.  
Temperature was monitored with a Barnant Instrument Co. Digi-
Sense (Cole Parmer Catalog # 8528-20) thermocouple thermometer.  
Rectal temperature was sensed with  a vinyl coated copper-
constantan thermocouple probe (Cole-Parmer Catalog # 8505-90).  
Esophageal temperature was monitored with an Instrument 
Laboratory 30 gauge  Capton-wrapped copper-constantan TC probe 
(IL# 53-30-513) attached to the obdurator of an esophageal 
gastric tube airway with heat-shrink tubing (i.e., the DEGTA).  
The patient's temperature descent during external cooling is 
presented in tabular form below and graphically at the end of 
this report.  

Table IV: Temperature Descent During External Cooling

Time       Rectal  C 	Esophageal  C	Observations
15:39	   N/A                   34.3          Start cardiopulmonary support
15:42      38.0                   N/A
15:46      38.0                   34.1
15:53      37.7                   34.5
15:58      35.9                   34.0
16:09      33.6                   32.0
16:19      31.6                   28.8
16:25      30.6                   27.1
16:30      29.8                   26.1
16:34      29.3                   N/A
16:42      27.4                   22.1
16:58      26.4                   20.3            Begin bypass.

	Shortly after the administration of the Maalox at 15:40 
moderate amounts of bile-tinged  fluid (clear with a yellow-
green cast) began draining from around the gastric tube in the 
obdurator of DEGTA.  This fluid continued to drain during 
Thumper support and eventually became tinged with Maalox (creamy 
white-greenish-yellow).  At no time was there any sign of 
gastric bleeding.  

	There was no evidence of  frank pulmonary edema such as 
blood-tinged pink foam in the mask of DEGTA as has been observed 
in many prior cryopreservation patients undergoing prolonged 
Thumper support.

Initiation of Extracorporeal Circulation and Total Body Washout

Femoral Cutdown

	Circulatory access for cardiopulmonary bypass was achieved 
via cut-down and cannulation of the right femoral artery and 
vein.  Femoral cut-down was begun at approximately 15:50.  The 
anatomical area for the cutdown had been determined and marked 
with a felt-tipped, indelible marker (Sharpie) prior to cardiac 
arrest by palpating for the femoral pulse between the pubic 
tubercle and the anrterior superior iliac spine.  An incision 
with a #10 scalpel blade was made over the area where the pulse 
was palpated (approximately at the midpoint between these two 
structures) beginning with the inguinal ligament and continuing 
parallel to the longitudinal axis of the leg for approximately 5 

	The femoral artery and vein were located rapidly and 
without difficulty.  Both the artery and vein were dissected 
free using blunt dissection and #2 silk ties placed on the 
proximal and distal exposures of both vessels.  The distal 
ligatures were tied to achieve occlusion.  There was a weak 
arterial pulse from the Thumper and moderate  distention and 
pulsation of the femoral vein.  There was very little capillary 
bleeding from the incision, but that which was present was 
observed to be bright red.

	An arteriotomy was made with a #11 scalpel blade and a 5.5 
mm Cardiovascular Instruments, Inc. stainless steel cannula with  
pressure monitoring side arm (see Figure 1) was introduced and 
secured with the proximal tie.   The side-arm of the cannula had 
been outfitted with a 19 g Intracath,  the tip of which 
projected approximately 1 cm beyond the tip of the cannula.  The 
Intracath was fitted with a Cobe 4-way stopcock, connected to a 
Cobe 8' pressure monitoring line which was flushed with saline, 
handed off the sterile field, and connected to a Bentley Trantec 
Model 800 pressure transducer (with Intraflow set-up) which was 
monitored with a Tektronix 414, EKG/pressure monitor.  The 3/8 
vinyl tubing to which the cannula was connected was then secured 
to the wound site by back-tying the distal arterial liagature 
around this tubing.

Figure 2: Femoral Arterial Cannula with side-arm for pressure 
measurement via inserted Intracath.

	Arterial pressure during Thumper CPS as measured via the 
arterial cannula Intracath set-up prior to initiating bypass was 
30 mmHg at 16:42.  A blood sample was  drawn at 16:50: the 
arterial blood was noted to be bright red and appeared well 
oxygenated.  Analysis of this sample disclosed the following 
(please see the graphic data at the end of this case report for 
the *hemodilution corrected* values for serum enzymes : 
hemodilution was corrected for using the serum total protein 
value from a sample collected premortem):

pH				7.136
pCO2				27.4
Na+				143 mM/L
K+				11.5 mM/L
Cl-				113 mM/L
Ca++				0.56 mM/L
Glucose 				6.0 mM/L
Urea Nitrogen			92 mg/dl
Creatinine			4.2 mg/dl
Magnesium			3.6 mEq/L
Phosphorus			20.7 mg/dl
Protein, Total			5.3 g/dl
Albumin			2.6 g/dl
Globulin, Total			2.7 g/dl
A/G Ratio     			1.0
Bilirubin, Total                        	 0.1 mg/dl
Alkaline Phosphatase	              145 U/L
Lactate Dehydrogenase          	 3267 U/L
GGT				220 U/L
AST				1694 U/L
ALT				479 U/L
Uric Acid			0.0 mg/dl
Iron, Total			394 mcg/dl
Iron Binding Capability	 	1007 mcg/dl
Iron Saturation			39%
Triglycerides			6 mg/dl
Cholesterol, Total		12 mg/dl
WBC				7.1 thous/mcl
RBC				2.4 mill/mcl
Hgb				7.9
HCT				24.4
MCV				24.4%
MCH				104 HL
MCHC				32.4%
RDW				16.7%
Platelets			91 thous/mcl

	Complete laboratory analysis of blood samples drawn during 
transport and extracorporeal support are presented graphically 
at the end of this document (with appropriate corrections for 
hemodilution in the case of serum enzymes).

	A veinotomy was performed using the same technique employed 
for the arteriotomy and a USCI type 1967  30 Fr. x 40 cm 
catheter was advanced until the catheter tip was well within the 
inferior vena cava and near the heart.  The catheter was then 
secured with the proximal tie and back-tied with the distal tie 
to prevent accidental dislodgment during bypass.  Venous blood 
was noted to be dark and de-saturated in appearance.

	The arterial perfusion line was connected to the arterial 
cannula tubing with a 3/8" straight connector with port, and the 
port fitted with a 4-way stopcock for evacuation of air.

	The venous return line was connected to the venous cannula 
with a 1/2" straight connector with port, and air was removed 
from the venous cannula  and venous line with a 35 cc plastic 

	External cooling from 38 C (rectal) at the time of cardiac 
arrest to 20.9 C (esophageal) at the start of bypass was at a 
rate of  0.20 C/min.

	Extracorporeal support was initiated at 16:58, 86 minutes 
following cardiac arrest, employing a Sarns 5M6002 roller pump, 
a custom tubing pack (see Figure 2), a Sarns 16323,  2000 ml 
flexible venous reservoir, a Sarns 16310 adult hollow fiber 
membrane oxygenator/heat exchanger and a Pall EC 1840 blood 
filter.  The extracorporeal circuit was primed with 1000 ml of 
Normosol-R pH 7.4, 500 ml Dextran-40 in normal saline, and 250 
cc of 20% mannitol in water.  Temperature was monitored with a 
YSI  42SL thermistor thermometer using a YSI 74868UO-88/U 
thermistor probe inserted into a Sci-Med temperature port placed 
in the arterial line where it exited the oxygenator.  (See 
Figure 3 for extracorporeal circuit diagram.)

Figure 3: Femoral-femoral bypass circuit.

	Bypass was begun at a blood flow rate of  1200 cc/min, a 
mean arterial pressure (MAP) of 100 mmHg and an oxygen flow rate 
to the oxygenator of 4 LPM.  Esophageal and rectal temperatures 
at the start of bypass were 20.9 and 26.4 respectively.

	At 17:02 blood flow was decreased to approximately 900 
cc/min because of the high MAP.  This maneuver reduced MAP to 88 
mmHg.  Arterial temperature at  that time was 9.5 C and 
esophageal and rectal temperatures  were 18.8 C and 25.0 C, 
respectively.   By 17:12 the arterial and venous blood were 
observed to be equally  oxygen-saturated (by eye) and bright red 
in appearance.  At that time the blood flow rate was 1050 
cc/min, MAP was 110 mmHg, arterial temperature was 9.0 C 
esophageal temperature was 11.1 C and the rectal temperature was 
20.8 C.  An arterial blood sample was drawn during bypass at 
17:18 and disclosed the following:

pH				7.014
pCO2				31.0 mmHg
Na+				140 mM/L
K+				9.2 mM/L
Cl-				114 mM/L
Ca++				0.58 mM/L
Glucose 				161 mM/L
Urea Nitrogen			76 mg/dl
Creatinine			2.8 mg/dl
Magnesium			2.9 mEq/L
Phosphorus			15.2 mg/dl
Protein, Total			2.5 g/dl
Albumin			1.4 g/dl
Globulin, Total			1.1 g/dl
A/G Ratio     			1.3
Bilirubin, Total                                      0.0 mg/dl
Alkaline Phosphatase	                78 U/L
Lactate Dehydrogenase                     1641 U/L
GGT				93 U/L
AST				876 U/L
ALT				270 U/L
Uric Acid			0.0 mg/dl
Iron, Total			204 mcg/dl
Iron Binding Capability		818 mcg/dl
Iron Saturation			25 %
Triglycerides			1.0 mg/dl
Cholesterol, Total		0.0 mg/dl

Total Body Washout (TBW)

  -- To Be Continued --

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