Perflurocarbons in Decompression Sickness Therapy Richard T Mahon
Perflurocarbons in Decompression Sickness Therapy Richard T. Mahon, MD Naval Medical Research Center Henry M Jackson Foundation
The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U. S. Government. I am a military service member (or employee of the U. S. Government). This work was prepared as part of my official duties. Title 17 U. S. C. § 105 provides that’ Copyright protection under this title is not available for any work of the United States Government. ' Title 17 U. S. C. § 101 defines a U. S. Government work as a work prepared by a military service member or employee of the U. S. Government as part of that person's official duties.
Decompression Sickness – Release of N 2 from tissue – Bubble Formation • Vascular Occlusion • Inflammation • Coagulation – Pain in joints – Neurologic Deficits – Cardiovascular Collapse – USUALLY 10 OR MORE MINUTES AFTER SURFACE
All you need to know ATA Atmospheres Absolute 33 feet of sea water Decompression Sickness and Nitrogen Narcosis Air Gas Embolism and Over inflation Oxygen Toxicity
The Real Issue • 1 ATA • 70 -155 men
DISSUB (Disabled Submarines) Kursk San Francisco Hartford
DISSUB DCS RISK
SRDRS
WHY PFCs • Carry O 2 • Eliminate Nitrogen • Small size • Surfactant Properties and Bubbles
Rodents SURVIVAL Spiess
Dromsky
Swine with Rapid decompression from 5 ATA with PFC and Oxygen Prebreathe Dainer 2007
NMRC Experience with Oxycyte NMRC Goals • Single PFC Product • Enough data to: – Support Animal Rule • Safety • Efficacy – Use in Treatment Oxycyte • Emulsion • perfluoro(tertbutylcyclohexane), (PTBH) • 60 % vol weight • Egg Yolk Phospholipd • 0. 2 -0. 4 , microns • T 1/2 of 17 H plasma (monkeys)
20 kg swine 200 fsw for 31 minutes • Oxycyte 5 cc kg • Mortality Decreased Aviation, Space, and Environmental Medicine Vol. 81, No. 6 June 2010
20 kg swine 200 fsw for 31 minutes • 3 cc/kg Oxycyte • Spinal cord pathology in DCS • No Change in Mortality
20 kg swine 6 ATA O 2 with 5 ml/kg Oxycyte • Seizure latency and duration NOT Changed Mahon, Eur J Appl Physiol DOI 10. 1007/s 00421 -013 -2720 -x. MAHON
Rats without seizures Saline 6 m. L/Kg PFC 3 m. L/Kg Seizure latency (Min) Oxygen Toxicity/Seizure * PFC 6 m. L/Kg Sali ne 5 ATA O 2 (min) PF C 3 m. L/k g 5 ATA O 2 JAPPL online 3 May 2012 Demchenko PFC 6 m. L/kg • Rats • CNS PO 2 increased at all doses • Seizure increased at all doses – Only statistically significant at 6 ml/kg and 5 ATA
MIXED GENDER DCS treated with Oxycyte followed by delayed recompression 200 fsw 31 minutes PFC v saline 4 cc/kg With 02 Navy TT 6 4 H post surface 24 H assessment Necropsy Animal Numbers 104 73 72 Mixed Gender Recompression safe No seizure
72% survival in Saline 67% survival 4 cc/kg/Oxycyte Chi-square; p=. 56
Sub-Groups
Chance for survival in males with PFC is 15% higher than NSS RR=1. 15 Chance for survival in females with PFC is 29% lower than NSS RR=0. 79 Chi-square; p=. 085
Findings • Mortality not improved in mixed gender • No seizures noted with TT 6 • Sub-group – Increase in female mortality?
Platelets • DCS associated with a decrease in platelets • Perflurocarbons also related to a platelet decrease – Nadir at 2 -3 days – Recovery in 7 -14
PFC Platelet Timeline If paralyzed @24 h, necropsy 1. Randomize Sham vs 31 min Dive to 180 fsw 2. Randomize Treatment with PFC or Saline ive std po ive 19 2 h std po 9 d Acclimitization 16 8 h VA pr P/7 ed 2 h ive r 1 h pr ed ive 1 h po std ive 24 h po std ive 48 h po std ive 72 h po std ive 96 h po std ive 12 0 h po std ive Blood Draws/Assessment Necropsy
PFC-Sham Saline-Sham PFC-Dive Saline-Dive
Sheep Treatment • Dive Profile 257 fsw for 31 minutes • Male 25 kg • Randomized to Oxycyte 5 ml/kg
P=0. 27 P=0. 21 P=0. 31 P=0. 15 Sorry this is actually 2: 15 H
What we know PFC in DCS Prevention • Multiple animal models show survival benefit PFC in DCS Therapy • Single study 5 cc/kg swine improves mortality • 3 cc/kg improves spinal cord pathology-swine • Possible survival benefitsheep
Is Oxycyte Good for DCS • Effective • Safe • Costs
Is it a good drug • Number needed to treat • NNT to prevent MI (NNT) mortality – ASA =77 – Statins=39 • At 5 cc/kg • NNT for heart attack – NNT (swine) =4 – NNT (sheep) =7. 7 – ASA =42 – Thrombolytic =43
Is it safe • At 5 cc/kg no increased seizure at 5 ATA Oxygen • At 5 cc/kg platelets acceptable • At 4 cc/kg recompression safe • Hemodynamics subject to interpretation • Seizure increased at 6 cc/kg BUT at nonrelevant O 2 levels • Mortality signal in female swine
Cost • PFC – 5 ml/kg= ($5 K) $20 K life • MI – TPA ($800)=$32 K life – ASA (pennies)= $1 life
How to Get to Happy Place • Viable product to allow single drug progression through FDA • Human Safety studies
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