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 discontinued. 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 medication). 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 Observations 02-04-94 07:00 N/A 3 sec. 148 82 40 N/A Glasgow Coma Score = 4 10:13 N/A N/A 163 84 41 40 03:30 N/A N/A 141 68 24 N/A 04:00 54/P N/A 143 68 26 N/A 05:00 56/P N/A 147 61 32 39 C Resp. labored, irreg. 06:00 70/P 3-4 143 59 31 N/A 07:15 48/P >4 142 58 34 N/A 07:45 48/P >4 142 59 36 N/A Resp. increasingly shallow 08:40 48/P >6 139 N/A 30 N/A 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 36.7 13:09 N/A N/A 129 81 . 21 N/A 13:26 N/A N/A 134 78 22 N/A 13:50 N/A N/A 134 88 17 N/A 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 Transport 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, M.D. 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 hose. 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 circuit. 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 cm. 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 syringe. 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 -- Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=2868