11 th Annual Cerebrovascular Symposium 5/11-12/2017. Hypertonic Use D E R E K C L A R K

Transcription

1 Hypertonic Use D E R E K C L A R K 1

2 Outline Types of hyperosmolar therapy Review Cerebral Na Physiology Differences between periphery and BBB Acute phase Subacute phase Chronic changes Hypertonic Saline Effects on Physiology Literature review pre and post 2007 Take away points 2

3 Types of Hyperosmolar Therapy Mannitol 0.5 to 1 g/kg bolus every 4+ hours Serum osmolality <320mMol/L Peak effect in 1 hour, starts in minutes and lasts several hours cautious in renal disease Rebound, hypotension (lower CPP), ATN, diuresis Hypertonic Saline Change in serum sodium Bolus vs continuous (2%, 3%, 7.5%, 23.4%) Meta-analysis shows equivalent to superior decrease in ICP vs mannitol Kamel, Critical Care Medicine

4 Cerebral Na Physiology Blood brain barrier Cerebral vascular endothelial cells, pericytes, basal lamina, and perivascular astrocytes Endothelial cells have tight junctions making solute transport transcellular vs paracellular (periphery) Allows for brain volume to be kept constant even with changes of vascular volume ATP pumps to regulate intact tissue Allows for osmolar gradients to be kept Passive permeability to water Acute change in plasma osmolality results in acute increases or decreases in brain water content Ertrner, Critical Care Med 2014, Ayus, Journal of Physiology

5 Cerebral Na Physiology 5

6 Cerebral Na Physiology Acute changes 1 Plasma hyperosmolar states result in acute decreases in brain water content Na, K+, Cl- accumulate in response to hyperosmolar states Initial intracellular response Only a portion of intracellular solutes Subacute changes 1 Day 1-7 of a hyperosmolar state Cells up regulate solutes termed idiogenic osmoles Amino acides, polyhydric alcohols, methylamines, sorbitol, myoinositol, etc Increase from % baseline Recovery phase day lag for osmoles to readjust Especially myoinositol Allows for a buffer in corrections of osmolarity 1. Heilig, Identification of idiogenic osmoles in brain Ertrner, Critical Care Med 2014, Ayus, Journal of Physiology 1996, 6

7 HTS Osmotic Effect Osmotic effect Shift of fluid from intracellular to interstitial and intravascular spaces 1 Most of the fluid mobilization is from the intracellular space and not the interstitial space 1 Shown that after immediate administration (7.5%) intravascular volume can increase by as much as 4x the volume given 2 Bolus of 7.5% at 4 hours can increase intravascular volume 750ml for every 1L given (vs 300ml vs NS 1L) 3 Reduction in intracranial pressure with HTS occurs mostly in the uninjured tissue 4 1 De Carvalho, Journal of Pediatria Sapsford, Journal of Royal Army 2003, 3 Jarvela Anesthesia 2003, Levine Critical Care Medicine

8 Cerebral Na Physiology Shapiro, J. Clin. Invest

9 Cerebral Na Physiology Carlos, Journal of Physiology 1996 The panels shows the brain tissue water content in control rabbits and rabbits with hypernatraemia for 1 h, 4 h and 1 week. The values after hypernatraemia and osmolality for 1 or 4 h are significantly less than both the control and 1 week values (P < 0-01), while the value after 1 week is not significantly different from control. 9

10 Cerebral Na Physiology Carlos, Journal of Physiology 1996 Brain intracellular concentrations of (Na+ K+) and idiogenic osmoles in hypernatraemic rabbits The panels show the brain intracellular [Na+ K+] and idiogenic osmoles in control rabbits and in rabbits with hypernatraemia for 1 h, 4 h and 1 week. All values are significantly greater than control (P < 0-01). 10

11 Cerebral Na Physiology Carlos, Journal of Physiology 1996 Brain osmolality and intracellular water content in rabbits before and after treatment for hypernatraemia The panels show the brain osmolality and water content in control rabbits, rabbits with untreated chronic (1 week) hypernatraemia, and rabbits in which hypernatraemia was lowered to normal values over 4, 8 or 24 h. All values in rabbits with treated hypernatraemia are significantly less than the value in rabbits with chronic hypernatraemia (P < 001) and significantly greater than control (P < 001). Shows increased intracellular water content with correction of Na. Cerebral edema 11

12 Cerebral Na Physiology Carlos, Journal of Physiology 1996 Brain intracellular concentrations of (Na +K+) and idiogenic osmoles in rabbits before and after treatment The panels show the brain intracellular [Na + K+] and idiogenic osmoles in control rabbits, rabbits with untreated chronic (1 week) hypernatraemia, and rabbits in which hypernatraemia was lowered to normal values over 4, 8 or 24 h. All values in rabbits with treated hypernatraemia are significantly less than the value in rabbits with untreated chronic hypernatraemia (P < 001). 12

13 HTS Cellular Osmotic Effect 13

14 HTS Overall Osmotic Effect HTS Bolus HTS Osmoles Idiogenic osmoles 72hrs to 1week Osmoles 14

15 HTS Data prior to 2007 Data derived in trauma To date goals are a ICP<20 and Cerebral Perfusion Pressure of 50 to 70mmHg These have shown to lower mortality 1 HTS vs Mannitol Less volume loss No human documentation of acute rebound ICP 1 Small cases suggest longer lasting effects and possibly more substantial response (23.4% and 7.5%) 2 1.Brain Trauma foundation guidelines 2007, 2. Valet Crit Care Med

16 HTS Data prior to 2007 Approach of a targeted sodium goal to reduce ICPs Most centers targeted a goal of mEq/l Most used bolus dosing Most administered HTS every 6 hours to the target range of Na Qureshi and colleagues (CCM 1998) Retrospective use of continuous infusion of 3% to Found lower ICP in 8 patients with TBI (P 0.03) and 5 postoperative patients (P 0.06) Mean ICP was reduced by mmhg, shift on CT was decreased Did not lower ICP in non-traumatic IPH or CVA 16

17 HTS Data prior to 2007 CT scan changes 17

18 HTS to reduce ICP prior to 2007 Standvik, Anaesthesia

19 HTS ICP reduction prior to 2007 Highlights Review Article 2009 Anesthesia Most studies used bolus dosing vs continuous infusions TBI 5 case controlled studies showed decreased ICP TBI 9 randomized controlled trials showed equality to mannitol Pre-hospital use (RCT paper by Cooper) showed no reduction in ICP. SAH 7 (5CC 1RCT) studies showed reduction in ICPs Stroke 2 studies both with poor power and quality 19

20 Brain Trauma Foundation 2007 Recommendations from the Brain Trauma Foundation Bolus Treatment for ICP Bolus HTS 7.2 to 10%, most from case series Reliably decreased ICPs Lowered ICPs in patients refractory to mannitol Repeat bolus dosing showed lowering ICPs without rebound phenomenon in TBI Reported rebound phenomenon for non-traumatic edema 20

21 HTS Literature After 2007 Bulger, JAMA 2010 Double blind RTC HTS 7.5% vs NS 6 month neurological outcome based on Extended Glasgow Outcome Scale and Disability Rating Score TBI patients - not in hypovolemic shock Randomized

22 Bulger, JAMA

23 Bulger, JAMA

24 HTS Literature After 2007 Wells, Critical Care 2012 Retrospective review Admitted with TBI to a neuroicu Had ICP monitors placed Primary Outcome was relationship between serum sodium and maximum ICP Secondary Outcomes were relationship between serum sodium and interventions for ICP control and acute effect of HTS on ICP during the 6 hours after each dose Na goal meq/l Bolus dosing mostly 3%, some bolus 7.5%, few continuous infusions n=81 24

25 Wells, Critical Care 2012 Shows a statistically significant difference in total number of interventions on days 2,3,5 and total days. When HTS bolus was excluded there was no difference. 25

26 Wells, Critical Care 2012 Conclusions No relationship between serum sodium and change in ICP HTS did raise the serum sodium The study did not show a significant change in ICP following a HTS bolus Good responders demonstrated a reduction in ICP that approached significance (p = 0.068) Good responders had higher scores on average on the Injury Severity Score Achieving a serum sodium between 145 and 155 may decrease the number of daily interventions 26

27 Adverse Effects of HTS Central pontine myelinolysis Acute heart failure 1 Pulmonary edema 1 Disrupted BBB may result in reverse osmosis with worsening edema 2 Theoretical risk that acute cerebral dehydration may cause shearing of bridging vessels (causing SAH) Acute hypotension 3 Hyperchloremic acidosis and hyperosmolar renal injury/failure 4 Hypokalemia secondary to urinary losses Delay or inability to diagnose CSW/SIADH 1. Suarez Cleveland Clinic Journal of Medicine White, Anesthesia and Analgesia 200, 3. Sapsford, Journal of Royal Army Medical Corps 2003,4. Kolsen-Peterson, Scandinavian Journal of Clinical Laboratroy Invest

28 Take Away Points HTS lowers ICPs in select patients Should be used as a rescue medication No evidence to support the use of HTS to prophylactically reduce the need for surgical intervention Target a change in sodium over a sodium number Advise only using for 3 days or less to avoid idiogenic osmoles causing increase of water content 28