By Francisco Gomez, MD1; Alyssa Polliti1; and Fawaz Al-Mufti, MD2
1Deparment of Neurology, University of Pennsylvania
1Department of Neurology, Rutgers - New Jersey Medical School
2 Department of Neurology and Neurosurgery, Westchester Medical Center at New York Medical College
The authors have no actual or potential conflict of interest in relation to the topics discussed in this column. This article may discuss non-FDA approved devices and “off-label” uses. The NCS and Currents do not endorse any particular device.
A device for administering volatile anesthetics in the NICU
Sedation in the Neuro-ICU
Sedation is an integral part of critical care patient management. This intervention improves patient comfort, decreases pain and anxiety, facilitates nursing care and improves ventilator synchrony. Additionally, sedation may be neuroprotective in the acute setting, especially in severely injured comatose patients, and also reduce sequelae, such as post-intensive care syndrome. GAβAergic sedatives generally reduce ICP, as well as suppressing seizures and cortical spreading depolarizations.
Intravenous medications, such as midazolam, propofol and dexmedetomidine, are staples in neurointensive care. However, said agents have limitations including hypotension, bradycardia, prolonged half-lives and metabolite accumulation varying by comorbidities, dose and duration of use. Therefore, volatile anesthetics may be a useful tool for sedation in the ICU given rapidity of onset and elimination, limited metabolism, cardioprotective and bronchodilatory effects.
Inhaled anesthetics, such as isoflurane and sevoflurane are emerging as alternatives for ICU sedation and offer promising applications in our specific patient population. Real-time monitoring of drug levels with the ability for ultra-rapid titration, onset and emergence are extremely attractive qualities. Evidence has shown isoflurane sedation may be achieved in seconds and maintained for >72 hours, as well as more rapid emergence than that from midazolam. Inhaled anesthetics may also prove beneficial in specific neurocritical settings, including cases where prognostication is required and rapid sedation offset ideal.
Several benefits have been observed. In one study, patients with SAH without initially normal ICP receiving isoflurane showed improved regional CBF with only a mild effect on ICP vs propofol controls. Another study found inhaled isoflurane led to effective sedation without significant rise in ICP in a population comprising ICH, SAH or acute ischemic stroke patients. Data has also suggested sevoflurane may have protective effects in sepsis and that Isoflurane suppresses cortical spreading depolarizations. Volatile agents have also been utilized with some success in refractory status epilepticus.
However, anesthetic gases are not widely available outside the operating room or routinely used for sedation given the logistical difficulties involved. Most ventilators do not readily accommodate a vaporizer. As not all the drug is absorbed by the patient, exhaled gas contains anesthetics and its management remains challenging in an open gas loop setting.
Inhaled Anesthetics in Status Epilepticus
Malignant status epilepticus (SE) consists of life-threatening, continual seizure activity lasting 24 hours or more despite therapy with IV anesthetic medications, or recurring SE upon the reduction or withdrawal of medications. Volatile agents are effective anticonvulsants. Though their mechanism of action is not completely understood, part of their effectiveness may be explained by GABAa receptor potentiation.
One recent review concluded there is level 4, class D evidence to support the use of isoflurane in refractory status epilepticus. Several case reports have reported success with isoflurane, and sevoflurane has been reported before to control super refractory status epilepticus. The latter was deployed with success in a patient with SRSE refractory to phenytoin, midazolam, sodium valproate, topiramate, levetiracetam, thiopentone and ketamine infusion for 24 hours.
The Anesthetic Conserving Device
Enter the anesthetic conserving device (AnaConDa), a simple yet elegant tool that solves these problems readily.
The AnaConDa easily adapts to a variety of ventilator circuits at the Y connector where a regular heat moisture exchanger connects. The device combines a standard syringe pump delivering the anesthetic into the breathing circuit of a standard ICU ventilator with a reflective filter to retain said gas on the patient side. Thus, as the patient inspires, incoming air actuates on the evaporator rod fed by the syringe pump filled with sevoflurane or isoflurane, and the resulting mixture is inhaled by the patient. As the patient exhales, up to 90% of the anesthetic gas is adsorbed onto the filter. Upon the following inspiration, said gas is released or “reflected” toward the patient.
The device possesses a gas monitor port on the patient side where inspired and expired CO2, and end-tidal concentration of the anesthetic are measured. The remaining 10% of the exhaled anesthetic is scavenged at the ventilator exhaust. Notably, standard syringe pumps are readily available and ease of use permits a gentle learning curve. A similar device, the MIRUS has emerged, with the ability to provide desflurane in the ICU. This device also utilizes a reflector filter. However, the MIRUS is somewhat more intricate, necessitating its own control unit that detects end-tidal concentrations and injects anesthetics during early inspiration, controlling anesthetic concentrations automatically.
There are several limitations to the AnaConDa device, notably it is not currently available in the United States, although it does hold CE approval in Europe.
Additionally, while the amount of utilized anesthetic is minimized versus an open loop or classical OR anesthesia machine, there still needs to be a gas scavenger connected to the ventilator exhaust port.
While the release of anesthetic gases into the environment is a concern, it has been found that AnaConDa + scavenging releases only 2-4ppm into the atmosphere, which is well within U.S. regulations for anesthetic gases and generally considered quite safe.
The AnaConDa increases anatomic dead space, hence there are minimal tidal volumes below that the device may be less effective, or increase PaCO2. Patients receiving lung protective ventilation, low flow, suffering from respiratory distress or presenting with high secretion burden are not ideal candidates for this device. While there is a paucity of data regarding inhalational anesthetics in the neurointensive care unit, this is confounded by the previous limited availability of this sedation modality in most centers.
As adoption spreads, it is likely that specific subsets of patients will benefit from this technique, especially given the rapid titration and emergence it offers.
- Farrell, R., Oomen, G. & Carey, P. A technical review of the history, development and performance of the anaesthetic conserving device “AnaConDa” for delivering volatile anaesthetic in intensive and post-operative critical care. J Clin Monit Comput 32, 595–604 (2018). https://doi.org/10.1007/s10877-017-0097-9
- Belda JF, Soro M, Badenes R, Meiser A, García ML, Aguilar G, Martí FJ. The predictive performance of a pharmacokinetic model for manually adjusted infusion of liquid sevofluorane for use with the Anesthetic-Conserving Device (AnaConDa): a clinical study.Anesth Analg. 2008 Apr;106(4):1207-14, doi: 10.1213/ane.0b013e31816782ff.
- Oddo, M., Crippa, I.A., Mehta, S. et al. Optimizing sedation in patients with acute brain injury. Crit Care 20, 128 (2016). https://doi.org/10.1186/s13054-016-1294-5
- Lehmann, Felix & Müller, Marcus & Zimmermann, Julian & Güresir, Ági & Lehmann, Victoria & Putensen, Christian & Vatter, Hartmut & Güresir, Erdem. (2019). Inhalational Isoflurane Sedation in Patients with Decompressive Craniectomy Suffering from Severe Subarachnoid Hemorrhage: A Case Series. Journal of Neuroanaesthesiology and Critical Care. 10.1055/s-0039-1693525.
- Andre Fernandes, Pharm.D, Morgen Schmitt Jaeger, Pharm.D., BCPS, Melissa Chudow, Pharm.D., BCCCP, Post–intensive care syndrome: A review of preventive strategies and follow-up care, American Journal of Health-System Pharmacy, Volume 76, Issue 2, 15 January 2019, Pages 119–122
- Kim H, Ryu J, Hwang JW, Do SH. Anesthetic management for cesarean delivery in a Guillain-Barré syndrome patient -A case report-. Korean J Anesthesiol. 2013;64(3):268–271. doi:10.4097/kjae.2013.64.3.268
- Wang H, Li P, Xu N, et al. Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke. Med Gas Res. 2016;6(4):194–205. Published 2016 Dec 30. doi:10.4103/2045-9912.196901
- Zhang EF, Hou ZX, Shao T, et al. Combined administration of a sedative dose sevoflurane and 60% oxygen reduces inflammatory responses to sepsis in animals and in human PMBCs. Am J Transl Res. 2017;9(6):3105–3119. Published 2017 Jun 15.
- Manatpon, P., Kofke, W.A. Toxicity of inhaled agents after prolonged administration. J Clin Monit Comput 32, 651–666 (2018). https://doi.org/10.1007/s10877-017-0077-0
- Tomar GS, Kapoor I, Mahajan C, Prabhakar H. Volatile Anesthetic for Management of Super-refractory Status Epilepticus. Indian J Crit Care Med. 2017;21(3):183. doi:10.4103/ijccm.IJCCM_235_16
- Romagnoli, S., Villa, G., Ricci, Z., Marra, F., & Amantini, A. (2018). Sevoflurane for the treatment of refractory status epilepticus in the critical care unit. Anaesthesia Cases, 6(1), 52–55. doi:10.21466/ac.sfttors.2018
- Zeiler, F. A., Zeiler, K. J., Teitelbaum, J., Gillman, L. M., & West, M. (2015). Modern Inhalational Anesthetics for Refractory Status Epilepticus. Canadian Journal of Neurological Sciences / Journal Canadien Des Sciences Neurologiques, 42(02), 106–115. doi:10.1017/cjn.2014.12