Source: http://www.google.com/patents/US6080538?dq=patent:5992892
Timestamp: 2013-12-08 20:25:30
Document Index: 607224590

Matched Legal Cases: ['art 80', 'art 110', 'art 80', 'art 2', 'art 2', 'art 1', 'art 1']

Patent US6080538 - Plasma like solution and methods of use - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Advanced Patent Search | Sign inAdvanced Patent SearchPatentsAqueous solutions comprising a polysaccharide oncotic agent, a physiologically compatible buffer, a simple hexose sugar, dissolved chloride salts of calcium, sodium and magnesium, and a dissolved organic salt of sodium are disclosed. The solutions are effective substitutes for blood and may be used to...http://www.google.com/patents/US6080538?utm_source=gb-gplus-sharePatent US6080538 - Plasma like solution and methods of usePublication numberUS6080538 APublication typeGrantApplication numberUS 08/896,823Publication dateJun 27, 2000Filing dateJul 18, 1997Priority dateJun 4, 1993Fee statusPaidAlso published asCA2164321A1, CA2164321C, CN1102851C, CN1127476A, DE69426879D1, DE69426879T2, EP0701455A1, EP0701455A4, EP0701455B1, US5571801, US5613944, US5698536, US5702880, US5723281, US5733894, US5747071, US5968726, US6110504, US6387612, US6406839, US6410218, US6444418, US20020009783, US20020012957, US20020025562, WO1994028950A1Publication number08896823, 896823, US 6080538 A, US 6080538A, US-A-6080538, US6080538 A, US6080538AInventorsJudith M. Segall, Paul E. Segall, Hal Sternberg, Harold D. WaitzOriginal AssigneeBiotime, Inc.Patent Citations (23), Non-Patent Citations (68), Referenced by (11), Classifications (32), Legal Events (3) External Links: USPTO, USPTO Assignment, EspacenetPlasma like solution and methods of useUS 6080538 AAbstract Aqueous solutions comprising a polysaccharide oncotic agent, a physiologically compatible buffer, a simple hexose sugar, dissolved chloride salts of calcium, sodium and magnesium, and a dissolved organic salt of sodium are disclosed. The solutions are effective substitutes for blood and may be used to preserve the biological integrity of the organs of a mammalian donor organism as shown by superior anatomical integrity of cryopreserved organs and tissues of subjects perfused with the solution. The solutions may be used for maintaining a partially or substantially completely exsanguinated subject at normal temperatures and at temperatures substantially below those normally maintained by a mammal and may be used in conjunction with hypobaric environments to maintain such partially or completed exsanguinated subjects alive without infusing blood back into the subject.
18. A method of substituting the circulating blood of a subject, the method comprising: administering to said subject a non-naturally occurring plasma-like solution consisting of:hydroxyethylstarch having an average molecular weight or at least about 150,000; Na+ in an amount ranging from about 70 to 160 mM; Cl- in an amount ranging from about 70 to 160 mM; Mg2+ in an amount ranging from about 0.3 to 10 mM; K.sup.+ in an amount ranging from about 0 to 5.0 mM; Ca2+ in an amount ranging from about 0.5 to 4 mM; a dynamic buffering system; and a simple hexose sugar; wherein said solution does not include a conventional biological buffer. 19. The method according to claim 18, wherein said hydroxyethylstarch is Hetastarch.
Many of the solutions used for initial perfusion with subsequent cold storage are based on the solutions of Collins et al. (1969) Lancet 2:1219 and Sacks et al. (1973) Lancet 1:1024. Ross et al. (1976) Transplantation 21:498 compared canine renal preservation following flushing and storage for 72 hours in various solutions. It was found that only kidneys preserved in a hypertonic citrate (HC) solution (comprising in part 80 mM K.sup.+, 55 mM citrate, 400 mOsmol/kg, pH 7.1) survived after 72 hours. The Collins and Sacks solutions in part contained 115-126 mM K.sup.+, 290-430 mOsmol/kg, pH 7.0-7.3. Wall et al. (1977) Transplantation 23:210 reports the hypothermic preservation of human livers for up to about 4 hours in a solution in part comprising 250 mg dextrose, and 15 mEq potassium phosphate. Bishop & Ross (1978) Transplantation 25:235 reported that renal function was preserved best in the HC solution of Ross et al. (1976) supra, rather than other available solutions. Fischer et al. (1985) Transplantation 39:122 found a new preservation solution for hypothermic ischemic storage (comprising in part 110 mM Na.sup.+, 115 mM K.sup.30 , 400 mOsm/kg, solvent D.sub.2 O, 110 mM HEPES) to be superior to other solutions in clinical use, including Collins, Sacks, and HC.
Among the solutions used for continuous organ perfusion, Belzer et al. (1985) Transplantation 39:118 reported a newly developed solution which preserved renal function when kidneys were perfused for 48 hours and stored for 24 hours (comprising in part 80 mM sodium gluconate, 22 mEq/l K.sup.+, 128 mEq/l Na.sup.+, 4.9 mM adenosine, 10 mM HEPES, 3.0 mM glutathione, 3.75% albumin, pH 7.45). Kallerhoff et al. (1985) Transplantation 39:485 examined the effect of temperature on pH of organs continuously perfused with two different solutions (Euro-Collins: 10 mM Na.sup.+, 115 mM K.sup.30 , 198 mM glucose, 406 mOsm/L, pH 7.2 at 20 180 mM histidine, 30 mM mannitol, 310 mOsm/L, pH 7.3 at 8 incubation temperatures between 5 maintained pH at consistently higher values than Euro-Collins solution.
The solution of the present invention uses normal biological components to maintain in vivo biological pH, a concept termed a "dynamic buffering system". The dynamic buffering system concept rests on the discovery by the inventors that compounds with no intrinsic buffering capacity in the biological range, such as lactate, capable of being metabolized in vivo, act with other solution components to maintain a biologically appropriate pH in an animal, even at hypothermic temperatures and at essentially bloodless conditions. The dynamic buffering system of the present invention depends in part on oxygenation and removal of carbon dioxide (CO.sub.2); and allows but does not require additional bicarbonate (NaHCO.sub.3). The dynamic buffer of the invention has no or substantially no ability to act as a buffer outside of a biological system, i.e., a dynamic buffer maintains pH in the biological range in vivo but not in a cell free environment. A component of the dynamic buffering system of the invention include a carboxylic acid, salt or ester thereof. What is meant by a carboxylic acid, salt or ester thereof is a compound having the general structural formula RCOOX, where R is an alkyl, alkenyl, or aryl, branched or straight chained, containing 1 to 30 carabons which carbons may be substituted, and preferably one of the carbon chains that compose the carbon chain of lactate, acetate, citrate, pyruvate, or other biological metabolites; and X is hydrogen or sodium or other biologically compatible ion substituent which can attach at the oxygen position, or is a short straight or branched chain alkyl containing 1-4 carbons, e.g., --CH.sub.3, --CH.sub.2 CH.sub.3.
Preparation of 10 L of Solution A. Into an appropriate container, add 80 g/L (or 800 g for 10 liters) of pyrogen-free Dextran 40 (Pharmachem or Pharmacia). Add deionized water, bringing the volume up to 6-9 liters. Dissolve the Dextran 40 completely by shaking. The following components may be added in any order, dissolving each completely before the addition of the next. The following reagents may be obtained from chemical supply houses; in this example the listed reagents were obtained from Sigma: NaCl (5.2 g/L), CaCl.sub.2 (0.29 g/L), MgCl.sub.2 (0.40 g/L), glucose (0.9 g/L), Tris (3.03 g/L), and sodium gluconate (6.54 g/L).
Preparation of Solution HL. To prepare 50 liters of solution HL (BioTime Hextend�-lactate), 3.0 kg of high molecular weight Hetastarch (HES) is added to 25 liters of water. Sufficient NaCl is added to bring the final NaCl concentration to 6.72 g/l. The solution is stirred until both the HES and NaCl are dissolved. The solution may be heated to 50 necessary. The total volume is brought to 45 liters and the following components are added and mixed until completely dissolved: CaCl.sub.2 �2H.sub.2 O 18.5 g; MgCl.sub.2 �6H.sub.2 O 4.5 g; KCl 11.0 g; glucose 45.0 g; and sodium lactate 4.03 ml/liter of a 60% (wt/wt) solution. The solution is brought up to a volume of 50 liters. The solution is filtered to remove undissolved material and placed in autoclavable containers and heated in an autoclave to a temperature of 120
Solution HLB. To each heat sterilized liter or HL solution is added 5 ml of a sterile 1 M solution of NaHCO.sub.3, medical grade, forming HLB solution (BioTime Hextend�-lactate-bicarbonate).
A fasted (overnight) female hamster, 40 grams, was injected, i.m., with 0.02 ml of Ketamine anesthetic (100 mg/ml). The hamster was immersed in crushed ice until its body temperature lowered to +14 then placed on a surgical stage and instrumented with EKG leads and a rectal temperature probe. The carotid artery and jugular vein were exposed surgically while the animal's body temperature was maintained between 10-14 arterial cannula was attached to tubing connected to a peristaltic pump. The tubing was filled with solution A, containing in addition 20 mM KCl. The venous cannula was capped until the animal's body temperature was lowered to 5 stage set at -1degree. C.
The animal stopped breathing on its own when its body temperature fell below 10 5 was pumped into the artery at a flow rate of about 0.3 ml/minute. Afterwards, 4.5 ml of a cryoprotective solution composed of solution A and in addition 4 mM KCl, 1.0M glucose, 4% propanediol (i.e. 1.8 g glucose +0.4 g propanediol per 10 ml solution) was infused. During perfusion, the venous effluent was collected. The animal's temperature was lowered gradually to 0 minutes following the onset of perfusion. At this time, more than 30% of the subject's blood volume had been removed. The heart continued beating until it eventually stopped. Following perfusion with the cryoprotective solution described in the preceding paragraph, the animal was placed in a sub-0 overnight.
The freezer temperature was kept at an average of -5 minutes after the animal was placed in the freezer, its rectal temperature lowered from 0 to -1degree. C. The animal's rectal temperature 12 hours later was -2.5.degree.C. The animal was then warmed to a temperature of about 2.5.degree. C. in a Quasar commercial kitchen microwave oven using 7 second pulses with the setting on warm. The pulses were generated 1 minute apart. Eighteen pulses were needed to thaw the animal.
An incision was made in the right groin region. A cannula was placed in the right femoral vein, and 0.02 ml of heparin solution (250 U/ml) was injected into the animal through the cannula which was then capped. Then the right femoral artery was cannulated. The cannula was connected to a luer-tipped segment of plastic tubing, and the tubing was passed through a peristaltic roller pump and into a reservoir containing solution A containing 0.05 M glucose. At the end of the tubing was inserted an 18 G hypodermic needle to which a mesh blood filter material was secured at the hub by a rubber "O" ring. The pump was turned on, and fluid in the reservoir was pumped through the tubing into the femoral artery of the animal. When the animal's temperature fell below 9 (at 20 breaths/minute) was initiated using 100% oxygen. The animal was cooled further to a rectal is temperature of 4 0.2M KCl was injected into the 24 G angiocath which was inserted in the femoral vein. This injection arrested the heart, and EKG signals ceased. The pump was turned on, and solution A was perfused into the artery at approximately 0.2 ml/min while venous effluent was collected. During the perfusion the animal's temperature dropped to near 1 of solution was perfused into the animal, the pump was turned off and the animal was kept surrounded by crushed ice in circulatory arrest for 2 hours. Then the animal was perfused with approximately 7 ml of whole blood (which was collected from other hamster blood donors) while the animal was gradually warmed using a desklamp. During the perfusion venous effluent was collected. The same volume pumped into the artery is collected as venous effluent. At 10 arrest for 3 hours and 11 minutes, heart beats were first observed upon monitoring EKG signals. Ventilation (6 breaths/minute) of the animal was then initiated using 100% oxygen. As the animal was further warmed and heart beats became stronger and faster, this rate was increased to about 15 breaths/minute. When the animal's temperature was above 28 the animal began to breathe on its own and became responsive. Perfusion was discontinued (the hematocrit reading 44%) and cannulas were removed and surgical wounds closed. This hamster remained alive in apparently normal health for many weeks after the experiment.
Following blood-substitution, the animal was placed on circulatory standstill for one hour and 40 minutes. At the end of the standstill period, 2 liters of ice-cold solution A was added to the circuit, replacing 2 liters removed as venous effluent. The minimum body temperature recorded was 2.8.degree. C. Rewarming was then begun. After 13 minutes of warming, the animalls body temperature reached 10 and 800 ml of a 1:3 mixture of blood and blood-substitute, followed by 450 ml of a 1:1 mixture, and finally, approximately 1 liter of whole blood was added to the circuit, replacing solution A.
In this example an 8 kg juvenile male baboon of the species Papio anubis was chilled and blood-substituted below 10 minutes. Prior to chilling and blood replacement, a 4F 60 cm Swan-Ganz arrow wedge catheter was placed in the pulmonary artery via the right femoral vein. This permitted measurement of the pulmonary arterial wedge pressure without performing a thoracotomy.
Procedure. The baboon was injected i.m. with 70 mg of ketamine. A 22 gauge 3 ml of 2.5% pentothal was injected i.v. The ape was then fitted with an endotracheal tube and moved to the x-ray room. It was placed on an x-ray table, and ventilated with a 1% mixture of isof luorane (Flether) in 100% O.sub.2, and a 4F 60 cm arrow wedge catheter was implanted in the pulmonary artery through the right femoral vein.
A blood--blood-substitute mixture was continuously removed as a venous effluent until 4 liters of solution A replaced the circulating solution. After 39 minutes of chilled blood substitution, the primate's temperature had declined below 4 pressure in the pulmonary circulation, which was readily measured, indicated that the circulation was good, and that the wedge pressure catheter was well placed.
After 50 minutes of blood-substitution below 1 temperature recorded was 2.9.degree. C. Rewarming was then begun, and after 28 minutes of warming, the animal's body temperature reached 10 replacing solution A.
Place a 25-30 Kg dog on partial cardiopulmonary bypass. Surface and core cool the dog to near the ice point (1-3 blood with solution HLB hypothermic blood substitute, described in Example 1. Retain the blood for transfusion during rewarming. Reduce the animal's body temperature to near the ice point (below 4 rewarm. Replace the blood substitute with blood with warming and revive the animal.
Preparation. Catheterize the dog by means of the right radial vein, injected iv with pentothal, then fit with an endotracheal tube and ventilate with isofluorane (or Flether) in 100% O.sub.2. Initiate a Ringer's lactate drip at a rate titrated to the dog's arterial blood pressure (approx. 40 ml/hr iv). Place the dog on a cooling blanket cooled with recirculating ice water. Catheterize the right carotid artery to allow for blood pressure (CAP) monitoring, and add a 3-way stopcock in-line to allow arterial blood sampling every 10-60 min. throughout the entire procedure. Insert a foley catheter for urine collection and measure the urine volume throughout the procedure. Implant a 2 lumen, 7 F, Swan Ganz wedge catheter via the right jugular vein or right femoral vein, which is fed through the right heart into the pulmonary artery. Use the distal port to measure pulmonary wedge pressure (PAW), the proximal port is used for central venous pressure (CVP). (If necessary CVP may be measured with a catheter inserted in one of the brachial veins.) Isolate the left femoral artery and vein and prepare for cannulation. Heparinize the animal (approx. 5,000 u). Insert a Biomedicus venous return cannula (15-19 F) in the femoral vein and a Biomedicus arterial cannula (12-15 F) in the femoral artery. Measure the activated clotting time (ACT) every 45 min. (until blood substitution) and adjust the heparin such that it remains greater than 400 sec. Attach a thermocouple approx. midway to an esophageal tube and insert the unit so that the tube enters the stomach. A second thermocouple is placed rectally. Attach ECG leads. Add Solu-Delta-Cortef (Upjohn, veterinary prednisolone Na succinate), 80 mg by iv injection. Coat the eyes with Terrimycin (or Lacrylube), and add DiGel (or Maalox, 20 ml) through the esophageal tube.
Blood Substitution. The circuit is primed with 2 liters of solution L (Example 1), and recirculated through the A-V shunt to ensure temperature-gas equilibrium. The cannulas are attached to the arterial and venous lines of the bypass circuit, and the lines remain clamped. The cooling blanket is wrapped around the patient who is surface cooled until a deep esophageal temperature of 35
After 4 liters have been exchanged (i.e. after the addition of 2 liters of solution L and 2 liters of solution HLB), 20 meq KCl will be injected via a stopcock on the secondary heat exchanger, to arrest the heart. During the exchange, the inflow is adjusted such that the PAW is kept below 5 mm Hg and the rate of efflux equals the rate of influx, i.e. as close to isovolemia as possible. At the end of the exchange the final reservoir level will be about 500 ml, the PAW below 5 mm Hg and the CVP less than 5 mm Hg. Flow will be adjusted such that isovolemia will be maintained (constant reservoir level and the above pressure levels, i.e. PAW&lt;5 mm Hg and CVP &lt;5 mm Hg).
Thirty three liters of blood substitute were exchanged. By the time the ice-point was approached, the hematocrit was far below itW. The animal's deep esophageal temperature was below 10 minutes, with a minimum recorded temperature of 0.7.degree. C. (Table 2).
TABLE 2__________________________________________________________________________REVIVAL OF AN ICE-COLD BLOOD-SUBSTITUTED DOG.              MAP HR PAW CVP FlowTIME SOLUTION      TE           TR               mmHg                  bpm                     mmHg                         mmHg                             L/min                                 pH PCO.sub.2                                       PO.sub.2                                           Na K Hct__________________________________________________________________________11:57 am       36.112:21 pm225 ml    35.2              129 133                     12  3HLB in &amp;225 mlbloodout@ 12:19 pm12:39 pm   32.6          34.8              134 141                     12  312:40 pm                          7.52                                 25.1                                    403                                       144 2.7                                              3412:52 pm                              7.41                                    34.7                                       581 151                                              3.1                                                371:35 pm1:36  32.2          32.9              141 132                     12  5   1.7pm onbypassw/1.05 LHLB1:40 pm    29.9          31.5              115 128                     10  3   1.71:43 pm    26.7          29.7              105 122                     8   3   1.81:46 pm                               7.36                                    37.1                                       719 143                                              2.6                                                241:50 pm5 L HLB      21.9          24.8              66  77 7   2   0.91:58 pm4 L HLB      18.5          20.1              19             1.12:00 pm4 L HLB      14.9          18.8              28             1.0 7.48                                    9.2                                       812 155                                              2.5                                                02:02 pm                               7.50                                    8.8                                        999+                                           165                                              3.6                                                02:04 pm    10.4          16.9              37             1.52:05 pm    9.9 16.2              372:08 pm4 L HLB      8.6 15.3              37             1.52:14 pm                               7.50                                    11.6                                        999+                                           159                                              4.22:16 pm2 L HLB      5.7 12.3              27             1.52:20 pm                               7.50                                    13.7                                        999+                                           151                                              5.12:22 pm    3.7 10.4              36             1.42:25 pm    3.3 9.8 35             1.62:27 pm    2.9 9.1 36     1       1.42:33 pm    2.1 7.4 37             1.42:44 pm2 L HLB                          7.54                                    11.6                                        999+                                           150                                              4.62:47 pm    1.4 4.8 36     3   1   1.32:50 pm    1.2 4.3 37     3   1   1.32:52 pm    1.2 4.2 37     3   1   1.32:59 pm2 L HLB      1.1 3.4 21             0.63:55 pm    0.9 2.3 22             0.44:00 pm                               7.63                                    9.6                                        999+                                           150                                              5.44:22 pm3 L HLB      1.1 2.1 20             0.35:00 pm2 L HLB      0.8 1.6 18             0.45:30 pm3 L HLB      0.85:50 pm                               7.48                                    11.0                                        999+                                           150                                              5.75:56 pm    1.8 1.8 19             0.46:04 pm    4.7 2.8 27             1.06:06 pm2 L HLB      6.6 3.3 27             1.1                06:08 pm2 L Half      9.7 4.1 30             1.1                20blood6:09 pm    9.9 4.26:11 pm    10.7          5.3 31  18 7       1.06:12 pm                               7.30                                    28.0                                       902 151                                              4.6                                                266:15 pm    13.8          6.7 30  24 13  2   1.16:25 pm    20.2          10.7              38     6   1   1.4 7.28                                    27.2                                       716 154                                              5.0                                                276:34 pm1 Lblood6:39 pm                               7.34                                    38.9                                       670 158                                              3.2                                                266:42 pm    29.2          18.1              60  143                     15  2   1.76:48 pm                               7.37                                    28.9                                       587 154                                              2.9                                                276:57 pm    32.8          32.2              132 161                     8   0   1.67:00 pm                               7.33                                    27.3                                       496 150                                              2.7__________________________________________________________________________ Te: Esophageal Temperature; Tr: Rectal Temperature, MAP: Mean Arterial Pressure; HR: Heart Rate; PAW: Pulmonary Arterial Wedge pressure; CVP: Central Venous Pressure
TABLE 3__________________________________________________________________________REVIVAL OF ICE--COLD BLOOD--SUBSTITUTED BABOON.           MAP HR ICP Flow            Plas-TIME    TE    TR        TB            mmHg               bpm                  mmHg                      L/min                          pH PCO.sub.2                                PO.sub.2                                   HLB                                      malyte*                                          Blood                                              Hct__________________________________________________________________________1:23 pm                                    1.6 L                                          (on �18                                      +   bypass                                      12.5 g                                          )                                      mannit                                      ol1:27 pm    31.3   32.8       33.2           60  83 9   2.21:30 pm    28.5   31.1       32.5           60  67 9   2.11:32 pm    23.4   29.0       30.9           50  45 8   2.21:35 pm    19.3   26.6       28.0           50  27 9   2.11:37 pm    18.0   25.5       26.5           50  24 11  2.21:38 pm    17.6   24.7       25.6           50  23 9   2.01:40 pm    16.8   23.7       24.3           50  25 8   2.01:44 pm    18.1   22.8       23.1           50  22 10  2.01:46 pm    18.0   22.2       22.3           50     8   2.1             0.3 L1:50 pm                                    0.1 L1:55 pm    12.2   19.3       18.2           50     4                7 L        02:02 pm    11.7   18.0       16.1           50     15  1.2 7.40                             27 530                                   2 L2:05 pm    12.7   17.5       15.1           40     9   1.0       3 L2:10 pm    11.3   16.9       14.1           40     9   1.32:14 pm    10.5   16.2       13.3           50     11  1.3 7.34                             17.1                                578.62:21 pm    9.6 15.0       11.9           50     11  1.32:25 pm    8.8 14.3       11.0           50     10  1.32:30 pm    7.9 13.4       9.9 50     10  1.3 7.37                             21.2                                7822:40 pm    6.4 11.7       8.0 50     9   1.32:49 pm    5.3 10.4       6.7 55     10  1.22:54 pm    5.4 9.8 6.3 50     7   1.23:18 pm    3.9 8.6 4.6 50     7   1.03:29 pm    3.2 7.8 3.8 50     8   1.03:32 pm    3.0 7.6 3.6 55     8   1.03:35 pm    2.9 7.4 3.5 50     7   1.03:37 pm    2.8 7.3 3.4        34:22 pm    3.7 10.1       4.8        14:24 pm    4.3 10.2       4.9 45     6   1.74:27 pm    6.5 10.4       6.4 55     8   1.0          2.2 L4:32 pm    8.3 10.5       7.7 60     8   1.1          3 L4:34 pm    9.0 10.6       8.5 65     10  1.04:36 pm    9.4 10.8       9.0 65     7   1.04:38 pm    9.9 10.9       9.4 60     6   1.04:39 pm    10.0   10.9       9.6 60     7   1.04:45 pm    11.4   11.4       11.2           75     10  1.04:47 pm    11.9   11.6       11.9           80     9   1.04:51 pm    13.2   12.2       13.5           85     7   0.94:53 pm    14.1   12.6       14.6           85  slow                  7   0.8 7.37                             14 7624:55 pm    14.6   15.2       15.9           90  slow                  6                   2 L     04:59 pm                                        0.3 L                                          1/10                                          blood5:01 pm                                        2 L                                          1/4                                          blood/                                          0.3 L                                          plasma5:05 pm    18.0   15.3       18.1           55             7.33                             22 224           25:16 pm                                        + 12.5                                          g                                          mannit                                          ol5:20 pm    24.6   20.0       24.5           44  fib                  12  2.15:24 pm                                        0.3 L                                          plama5:25 pm    25.0   20.9       25.2           44  fib                  13  2.0 7.30                             25.3                                5935:36 pm                                        0.4 L                                              12                                          blood                                          + 12.5                                          g                                          mannit                                          ol5:37 pm    26.7   22.4       28.7           45  fib                  12  2.05:43 pm                                            0.3 L                                          blood5:55 pm    32.0   24.8       32.8           45  fib                  10  2.25:57 pm    32.2   25.3       32.9           45  fib                  8   2.26:10 pm    35.3   28.8       36.6           55  beat                  116:13 pm    36.3   30.3       36.8     76:23 pm    37.3   33.7       36.2           60   7 7   1.3 7.34                             28.2                                435           176:34 pm                        7.39                             31.9                                322           206:36 pm                                        0.3 L                                          plasma__________________________________________________________________________ Te: Esophageal Temperature; Tr: Rectal Temperature; Tb: Brain Temperature MAP: Mean Arterial Presure; HR: Heart Rate; ICP: IntraCranial Presuure
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