Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
What Works for Brain Protection?
INTRODUCTION
Despite recent advances in anesthesia techniques and monitoring measures, intraoperative and postoperative neurologic events remain the most devastating complications that continue to concern anesthesia providers. Even without any significant intraoperative events, there is a considerable risk for cerebral ischemia in specific surgical populations, such as in cardiac surgeries and vascular surgeries.
The neurologic sequelae range from frank stroke to cognitive dysfunction. The incidence of perioperative stroke is reported from 1.6% to 5.2% in coronary artery bypass grafting (CABG) and from 0.25% to 7% in carotid endarterectomy (CEA), whereas the incidence of cognitive dysfunction ranges from 24% to 57% at 6 months after cardiac surgery.
There is a substantial amount of interest in preclinical and clinical research to identify neuroprotective strategies; however, most of the clinical trials have resulted in disappointment, and there are no formal guidelines based on the strongest clinical evidence. This is thought to be because of the complexity of the mechanism in cerebral ischemia.
Most anesthesia providers strongly agree that maintaining adequate cerebral oxygenation and perfusion pressure is the most effective and important strategy in neuroprotection. Historical clinical evidence also advocates for avoiding deleterious factors in the event of ongoing cerebral ischemia or in higher-risk populations.
OPTIONS
Neuroprotective strategies can be classified into two concepts: passive, which refers to the avoidance of deleterious factors; and active, which refers to the application of beneficial interventions. Hans and Bonhomme proposed categorizing the neuroprotection measures into the following areas: physiology, anesthetics, nonanesthetic pharmacologic agents, and preconditioning. Along with these strategies, the role of monitoring in specific surgical populations will be discussed.
- 1.
Physiology: Avoidance of hyperthermia, hyperglycemia, cerebral hypoxia, and hypoperfusion.
- 2.
Anesthetics: The use of certain anesthetics that are potentially neuroprotective because of reduction of energy requirements.
- 3.
Pharmacology: The use of potentially neuroprotective agents that can block the pathways of neuronal cell death. This may include N -methyl- d -aspartate (NMDA) receptor antagonists, excitatory amino acid (EAA) receptor antagonists, and erythropoietin (EPO).
- 4.
Preconditioning/postconditioning: The use of physiologic or pharmacologic alterations that could mimic ischemic preconditioning/postconditioning for high-risk populations.
- 5.
Monitoring: The use of epiaortic echocardiographic scanning to manage severe atherosclerotic disease by altering the surgical technique and near-infrared reflectance spectroscopy (NIRS) for assessment of bifrontal regional cortical oxygen saturation (rSO 2 ) in cardiac surgery.
EVIDENCE
A number of studies have evaluated neuroprotective strategies and outcomes in the area of physiology, anesthetics, pharmacology, and monitoring ( Table 43.1 ).
TABLE 43.1
Overview of Major Clinical Studies Evaluating Neuroprotective Strategies and Outcome
| Study (Year) | Number of Subjects | Patient Population | Study Design | Intervention | Control | Outcomes |
|---|---|---|---|---|---|---|
| Physiology | ||||||
| Bernard (2002) | 273 | Comatose survivors of out-of-hospital cardiac arrest | Prospective randomized | Mild hypothermia | Normothermia | Favorable neurologic outcome |
| Kammersgaard (2002) | 390 | Acute stroke | Observational | Hypothermia (≤37°C) | Hyperthermia (>37°C) | Low admission temperature is an independent predictor of good short-term outcome |
| Grigore (2001) | 165 | CABG with CPB | Prospective not randomized | Slower rate of rewarming | Conventional rewarming | Better cognitive performance at 6 weeks |
| Gentile (2006) | 960 | Acute ischemic stroke | Retrospective | Normalization of BG (<130 mg/dL) during first 48 hr | Hyperglycemia (BG ≥130 mg/dL) | Associated with a 4.6-fold decrease in mortality risk |
| Vicek (2003) | 372 | Acute ischemic stroke | Retrospective | Lowering DBP more than 25% from admission value | Maintained DBP | Associated with 3.8-fold increased adjusted odds for poor neurologic outcome on day 5 |
| Ahmed (2003) | 201 | Acute ischemic stroke | Retrospective | Lowering DBP with nimodipine | Maintained DBP | Worsened the neurologic outcome in nontotal anterior circulation infarct |
| Gold (1995) | 251 | CABG with CPB | Prospective randomized | High MABP (80–100 mm Hg) during CPB | MABP 50–60 mm Hg during CPB | Fewer myocardial and neurologic complications |
| Anesthetics | ||||||
| Michenfelder (1987) | 2223 | Carotid endoarterectomy | Retrospective chart review | Isoflurane | Enflurane, halothane | Lower critical CBF (10 mL/100 g/min) vs. 15 in enflurane and 20 in halothane; lower incidence of EEG ischemic change (18% vs. 26% in enflurane and 25% in halothane) |
| Messick (1987) | 6 | Carotid endoarterectomy | Prospective single-arm | Isoflurane | Halothane | Lower critical CBF (less than 10 mL/100 g/min) vs 18–20 in halothane |
| Kanbak (2004) | 20 | CABG with CPB | Prospective randomized | Isoflurane | Propofol | Alleviated increase of S-100 beta protein |
| Hoffman (1998) | 12 | Middle cerebral artery occlusion | Prospective randomized | Desflurane | Etomidate | Increased brain tissue P O 2 and attenuated acidotic change |
| Laitio (2016) | 110 | Out-of-hospital cardiac arret | Prospective randomized | Inhaled xenon and hypothermia | Hypothermia only | Less white matter damage. No significant difference in neurologic outcomes or mortality at 6 months |
| Mitchell (1999) | 65 | Left heart valve operation | Prospective randomized | Intravenous lidocaine | Placebo | Fewer incidences of decreased neuropsychologic performance |
| Wang (2002) | 118 | CABG with CPB | Prospective randomized | Intravenous lidocaine | Normal saline | Decreased the occurrence of early postoperative cognitive dysfunction |
| Klinger (2019) | 478 | Cardiac surgery | Prospective randomized | Intravenous lidocaine | Placebo | No difference in cognitive function at 6 weeks and 1 year |
| Hudetz (2009) | 78 | Cardiac surgery | Prospective randomized | Ketamine | Placebo | POCD was attenuated at 1 week |
| Pharmacology | ||||||
| Arrowsmith (1998) | 171 | CABG with CPB | Prospective randomized | Remacemide | Placebo | Overall postoperative change (reflecting learning ability in addition to reduced deficits) was favorable in treated group |
| Mathew (2004) | 914 | CABG with CPB | Prospective randomized | Pexelizumab | Placebo | Decreased visuospatial function impairment but not overall cognitive dysfunction |
| Ehrenreich (2002) | 40 | Acute ischemic stroke | Prospective randomized | Recombinant human erythropoietin | Saline | Improvement in clinical outcome at 1 month |
| Bhudia (2007) | 350 | Cardiac surgery with CPB | Prospective randomized | Magnesium sulfate | No intervention | Improved short-term neurologic function |
| Saver (2015) FAST-MAG) |
1700 | Stroke | Prospective randomized | Magnesium sulfate | Placebo | No significant difference in 90-day disability outcomes |
| Pandharipande (MENDS) |
106 | Mechanically ventilated in ICU | Prospective randomized |
Dexmedetomidine | Lorazepam | More days alive without delirium or coma, more time at the targeted level of sedation |
| Su (2016) | 700 | Elderly after noncardiac surgery | Prospective randomized | Dexmedetomidine | Placebo | Incidence of postoperative delirium was significantly lower in dexmedetomidine group for 7 days |
| Ono (2017) | 50 | Acute cerebral infarction | Prospective randomized | H 2 gas inhalation | No intervention | More marked improvement in MRI and neurologic status in first 2 weeks |
| Preconditioning/Postconditioning | ||||||
| Meng (2012) | 68 | Symptomatic intracranial arterial stenosis | Prospective randomized | Bilateral upper limb ischemia followed by reperfusion | No intervention | Incidence of recurrent stroke was reduced in treated group |
| Royse (2000) | 46 | CABG with CPB | Prospective not randomized | Epiaortic echocardiography and exclusive Y graft | Digital palpation and aorta-coronary operations | Less incidence of late neuropsychologic dysfunction |
| Murkin (2007) | 200 | CABG with CPB | Prospective randomized | Cerebral regional oxygen saturation (rSO 2 ) monitoring and treatment protocol | No intervention | Avoids profound cerebral desaturation and is associated with fewer incidences of major organ dysfunction |
| Bennett (2020) | 182 | Cardiac Surgery with CPB | Prospective randomized | Cerebral oximetry with interventions to maintain rSO 2 | No intervention | No difference in neurologic outcomes nor hospital LOS. Significant improvement in ICU LOS. |
BG, Blood glucose; CABG, coronary artery bypass grafting; CPB, cardiopulmonary bypass; DBP, diastolic blood pressure; EEG, electroencephalogram; MABP, mean arterial blood pressure.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here