key: cord-0728922-xglhx928
authors: Ghia, Samit; Lazar, Michael; Epstein, Jonathan; Bhatt, Himani V.
title: “ANESTHESIA STAT” TO INTUBATE A COVID-19 PATIENT: IMPLICATIONS FOR THE ANESTHESIOLOGIST
date: 2020-05-15
journal: J Cardiothorac Vasc Anesth
DOI: 10.1053/j.jvca.2020.05.016
sha: 9d7e8f5926b65090b310d1ef95b4cc1058c2c405
doc_id: 728922
cord_uid: xglhx928

nan

In December 2019, a pneumonia outbreak of unknown etiology spread through China. By February 2020, the World Health Organization (WHO) formally identified the cause as coronavirus disease 2019 (COVID-19) [1] . Due to its high transmissibility and rate of hospitalization, the novel virus created a pandemic [2] .

Health care workers around the globe are confronting this disease on many fronts. The anesthesiologist, in particular, is encountering this virus in the operating room (OR), intensive care unit (ICU) and during urgent or emergent intubations. Patients are primarily presenting with pulmonary manifestations, frequently requiring advanced oxygen support including an advanced airway [3] . Due to the highly contagious nature of COVID-19, most of the concern for medical personnel has focused on minimizing exposure during the intubation. Prophylactic measures have included donning adequate personal protective equipment (PPE) and using video laryngoscopes to maintain distance from the airway [4] . Also, many Anesthesiology departments have implemented dedicated Intubation Teams to allow for effective airway management and decrease unnecessary exposure.

Although reducing exposure of medical personnel is of obvious importance, there has been a dearth of literature discussing clinical strategies during the induction and intubation of COVID-19 patients. Importantly, optimizing the intubation process could reduce exposure by reducing time at the bedside. In this editorial, we will briefly review the pertinent physiology of COVID-19, understand the anesthetic implications and provide a number of strategies to efficiently and safely induce and intubate a COVID positive patient.

COVID-19 is caused by a coronavirus genetically related to the virus that caused the SARS outbreak of 2003. Most patients present with respiratory symptoms ranging from nonproductive coughs with fever, to shortness of breath and hypoxia in severe cases. The virus, which is primarily contracted through respiratory droplets, possesses spike proteins that bind angiotensin converting enzyme-2 (ACE-2) receptors. These receptors are located in the lower respiratory tract and serve as the entry point for SARS-CoV-2 [3] . Histologic analysis demonstrates diffuse lymphocytic infiltrates, hyaline membrane development and abnormal pneumocytes [5] . These may be the result of direct cellular injury and/or activation of an immune cascade. Patients can develop hypoxic respiratory failure secondary to pneumonia, pneumonitis and/or acute respiratory distress syndrome (ARDS) [3] .

Unfortunately, COVID-19 is not solely a pulmonary disease. Patients have presented with cardiac symptoms and an acute decrease in their ventricular function. Myocardial injury, indicated by cardiac biomarkers, has been seen in the setting of a cytokine storm or as the primary manifestation. Postulated mechanisms of a viral cardiomyopathy include myocyte apoptosis secondary to hypoxia, cytokine storm induced myocardial injury, or direct infection from ACE-2 activity [6] . Lastly, pulmonary vasoconstriction secondary to significant hypoxia and hypercarbia could exacerbate any right ventricular dysfunction.

ACE-2 receptors, present on cardiomyocytes, are also prevalent on endothelial cells throughout the body. Attachment to the receptor may result in down-regulation of ACE-2, causing unopposed angiotensin II activity. ACE-2 counterbalances angiotensin II by promoting anti-inflammation, anti-oxidation and vasodilation. Unchecked angiotensin II could injure tissues via a pro-inflammatory, pro-thrombotic, vasoconstrictive state [7] . Tissue injury could result in endothelial dysfunction mirroring that which is seen in septic or distributive shock. The autonomic nervous system is immensely intertwined in the response to sepsis. The parasympathetic system works by an efferent inflammatory reflex to attenuate the inflammatory response. On the other hand, the adrenergic sympathetic system is pro-inflammatory via catecholamines. However, after an initial surge, stores of catecholamines can become depleted resulting in septic shock [8] .

The kidneys are also implicated, possibly due to tubular epithelial expression of ACE-2.

Acute kidney injury (AKI) is occurring in a significant percentage of hospitalized patients and is associated with increased mortality. AKI is demonstrated by elevated creatinine and blood urea nitrogen (BUN) levels. The exact mechanism of renal injury is unknown, but could be due to direct viral injury, hypoxia, decreased renal perfusion, or the systemic inflammatory response [9] .

Numerous pharmacologic strategies can be implemented during induction and intubation of COVID-19. Any strategy must incorporate a rapid sequence induction to minimize exposure and avoid aspiration. Although no studies have evaluated or determined ideal agents for inducing these patients, much can be inferred from the disease's pathophysiology. Categories of pharmacologic agents include analgesics, amnestics, and paralytics.

Opioids, such as fentanyl, hydromorphone and morphine, are the most commonly used analgesic in anesthetic inductions. Their administration has little influence on hemodynamics, with the most common effect being bradycardia secondary to sympathetic blunting. However, at larger doses, opioids have the potential to depress myocardium, and morphine can result in hypotension from histamine release [10] . Histamine release can also cause bronchospasm and large doses can lead to chest wall muscle rigidity, both of which could impair adequate ventilation and oxygenation [11] . Opioids are an option in inducing COVID-19 patients; however, large fentanyl doses have been associated with post-induction hypotension, possibly due to sympathetic attenuation, which could be significantly pronounced and devastating in septic patients [12] .

Benzodiazepines, like midazolam, have even fewer cardiac side effects than opioids.

Midazolam can lead to a slight reduction of systemic vascular resistance (SVR) when given at high doses (0.2-0.3 mg per kg); however, these doses are rarely used in inductions [10] . In septic patients, the decrease in SVR could lead to dramatic hypotension [12] . Benzodiazepines should be cautiously used in patients with renal disease, since they have been associated with a higher risk of acute kidney injury (AKI) in ICU patients [13] . Midazolam could serve as a good induction agent for COVID-19 intubations because of its fast onset of action and hemodynamic profile.

Ketamine, unlike other agents, is a sympathomimetic that indirectly causes sympathetic stimulation via a release of catecholamines. Epinephrine and norepinephrine release can result in an elevation of blood pressure, cardiac output and heart rate at the cost of increased myocardial oxygen demand [10] . However, ketamine can directly depress myocardial function, especially in states of catecholamine depletion and at larger doses necessary for induction of anesthesia [10] .

Ketamine does have many benefits as an induction agent. Its sympathomimetic effect induces bronchodilation, which can improve lung compliance and reduce airway resistance [11] . In addition, Ketamine does not suppress respiratory drive. An animal study demonstrated that ketamine attenuated renal inflammation seen with hypoxia [13] . In sepsis or septic shock, ketamine can be protective against inflammation, reduce nitric oxide production, and decrease cardiac dysfunction, all of which prevent hemodynamic instability [12] . Ketamine could be a good agent for COVID-19 patient inductions; however, the anesthesiologist must be wary of cardiac failure with induction doses, especially if there is any preexisting history of cardiac disease or concern for viral cardiomyopathy.

Propofol can depress sympathetic vasoconstriction and reduce calcium influx, causing profound vasodilation and depress myocardial contraction respectively, especially at the high doses used for induction and intubation. It suppresses the sympathetic tone more than parasympathetic activity, potentially leading to significant bradycardia [10] . Propofol also acutely depresses the respiratory drive, possibly worsening the hypoxia or hypercarbia prior to intubation. On the other hand, propofol can bronchodilate and decrease hypoxic pulmonary vasoconstriction (HPV) [11] . Propofol, due to its antioxidant and anti-inflammatory properties, seems to be renal-protective by attenuating ischemic reperfusion injury and reducing the incidence of AKI [13] . In sepsis, however, the use of propofol can be associated with significant post-induction hypotension. Also, cardiac inotropy and lusitropy can decrease by approximately 40% in severe sepsis and should be avoided or used cautiously in COVID-19 patients [12] .

Etomidate does not inhibit sympathetic activity nor depress myocardial contractility with induction doses. However, even a single dose can induce adrenocortical suppression [10] . Also, Bastin et al reviewed septic patients receiving etomidate for intubation and noted significant hypotension [14] . Etomidate has minimal respiratory side effects; however, coughing can occur, potentially increasing viral aerosolization [11] . Regarding the renal system, an animal study showed etomidate was less protective against tubular injury [13] . Etomidate can be considered for induction in COVID-19 patients because of its safer cardiac profile; however, hemodynamic instability due to catecholamine depletion and adrenal suppression are important considerations in these patients [12] .

Emergent airway intubation most often requires paralysis. Paralysis is specifically helpful in COVID-19 patients due to cessation of breathing and coughing, which decreases aerosolization of the virus during the procedure. Most commonly used agents in modern practice include rocuronium, vecuronium, cisatracurium, and succinylcholine.

Nondepolarizing muscle blockers (NMBs) can cause some cardiovascular effects secondary to histamine release; however, this does not occur with the use of rocuronium, vecuronium and cisatracurium [10] . On the other hand, the depolarizing muscle relaxant succinylcholine can have more exaggerated cardiovascular effects compared to nondepolarizing agents. Malignant arrhythmias can occur secondary to muscarinic interaction at the sinus node or from hyperkalemia release at extrajunctional receptors [10] . Succinylcholine, which also causes histamine release, can induce bronchoconstriction [11] . The NMB used is based on practitioner preference and should account for potential side effects.

Any discussion of equipment must be focused on reducing viral exposure. Equipment can be divided into provider and procedure specific. Provider equipment primarily encompasses PPE, which at a minimum, must include an N-95 mask, face/eye protection, cap or hat, 2 sets of gloves and a gown. Shoe covers can be utilized if available. The face/eye protection can be a shield or goggles but should be checked for any smears or streaks to avoid visual disturbances.

All PPE must be properly donned in an area outside the patient room and partially doffed inside patient or ante room with the exception of the N-95 mask and one set of gloves.

Procedural equipment should keep the intubation process simple, straightforward and easy to replicate. Video laryngoscope is ideal to maintain distance from the airway and also reduce potential airway difficulty. If available, a handheld video laryngoscope may also be considered due to its smaller size and ease of handling compared to traditional video laryngoscopes. Also, handheld laryngoscopes may be easier to clean and can be used as a traditional MAC blade if needed. An endotracheal tube (ETT) should be loaded with a stylet and syringe for cuff inflation. A smaller, back-up ETT should be readily available for unanticipated airway difficulties. Induction medications should be drawn up and connected to stopcocks with an extension to easily facilitate injection to a proximal port of the intravenous (IV). All preparations should be done prior to entering the room to shorten exposure time. Any superfluous equipment should be kept outside the COVID-19 patient room to avoid unnecessary contamination or waste. Drapes or clear boxes with access for intubation can be utilized at the head of the bed to minimize exposure. Any additional strategy to minimize exposure should be tested and properly understood by the anesthesiologist, because some of these "tricks" could potentially interfere with the intubation and increase the time in the room.

In addition to procedural equipment, additional preparations are needed for an emergent COVID intubation. The team that will enter (ie. Anesthesiologist, nurse, respiratory therapist) should be determined outside the room. Also, when possible, the ventilator should be set up and ready in the room prior to the anesthesiologist entering the room. An ambu-bag with mask and a viral filter inserted distally and functioning suction line and intravenous line should be checked and readily available.

Many Anesthesiology departments have deployed dedicated Intubation Teams, separate from the OR/call teams to allow for expedited airway management while decreasing unnecessary exposure. Using the same personnel on these shifts allows teams to develop familiarity with one another and develop a rhythm when dealing with the novel challenges that are presented by intubation of patients with COVID. Most of these teams function in a buddy system with an attending anesthesiologist plus a CRNA or resident and scheduled in shifts (8hr or 12hr) to allow for highest skilled individuals for airway management while preventing exhaustion.

When called to emergently intubate these patients, the anesthesiologist must appreciate the pathophysiology of this virus and the effect it can have on multiple organ systems. Prior to entering the COVID-19 patient's room, a review of the chart or a discussion with the primary team should include past medical history, current hemodynamic state, pertinent labs and findings, current medication regimens and the need to intubate over other strategies to improve oxygenation and ventilation.

After ensuring intubation is required, the anesthesiologist should determine appropriate pre-induction monitoring. COVID-19 has worse outcomes in patients with comorbidities such as hypertension and heart failure and these patients are more likely to require mechanical ventilation. Beyond basic monitoring (i.e. pulse-oximetry, non-invasive blood pressure, electrocardiography (ECG) and capnography), patients with significant cardiovascular disease, virus-induced cardiomyopathy or hypotension secondary to distributive shock may need an arterial line, central line and/or defibrillator pads. Induction and intubation can cause significant hemodynamic instability and these additional monitors could contribute to a more stable procedure and allow for quickly initiating vasopressor infusions and assisting in advanced life support care (ACLS), if needed.

In addition to monitoring, the anesthesiologist should check with the primary team and nursing about sedation plans after the intubation. No intubation should be attempted without confirming that a functioning IV is available and suction with a yankauer is prepared. Lastly, one must confirm with respiratory therapy about a connected ambu-bag with a viral filter in-line and a configured ventilator. All these steps streamline the process and minimize time in the room and should be completed prior to entering the patient room.

Upon entering the COVID-19 patient room, after securing appropriate personal and procedural equipment, the anesthesiologist should quickly move to the head of the bed while assessing the patient's current oxygenation and airway. Most, if not all, of these patients will have advanced oxygen delivery, such as a non-rebreather mask, high flow nasal cannula or bilevel positive airway pressure. The anesthesiologist should not remove the patient's current therapy in favor of ambu-bag to avoid increased aerosolization. The World Health Organization has suggested using any mode to preoxygenate for five minutes [3] . If airway concerns are elicited upon quick assessment, a fellow anesthesia provider (ie. buddy) should enter to provide assistance. If the brief airway exam does not raise any alarms, the colleague should wait outside and act as a runner in case additional resources are necessary. Assuming a straightforward airway, medications may be injected by the anesthesiologist via the extension tubing. The respiratory therapist should remain near the ventilator and patient head in case cricoid pressure or any assistance is necessary [4] . Table 1 summarizes our recommendations when approaching a COVID-19 positive intubation.

In our experience at an institution in New York City with a census high in COVID patients, the ideal anesthetic was one which facilitated quick intubation and reduced intervention post-intubation. By the time patients require intubation, many had progressed to the septic phase of COVID-19. We noted the need for significantly decreased anesthetic to successfully intubate these patients while maintaining hemodynamic stability. Rapid sequence strategies utilizing benzodiazepines with rocuronium resulted in a smooth and hemodynamically stable intubation.

Midazolam doses commonly used were between 4-6 mg, approximately 0.05 mg/kg and rocuronium doses of 1.2 mg/kg. Analgesia was not a concern as most patients had no tachycardic response to intubation. Propofol and etomidate usage was noted to have greater hemodynamic instability, possibly due to catecholamine depletion consistent with severe sepsis.

Rocuronium was preferred over succinylcholine because COVID-19 patients have long ventilatory courses and ventilator synchrony improves oxygenation and ventilation.

Succinylcholine was also avoided because many patients had AKI and elevated potassium levels.

Cisatracurium is a theoretically ideal agent in renal injury patients, but, as the timeline to consider extubation is a long one, the use of Cisatracurium may not be warranted. As the most common hemodynamic derangement was hypotension, phenylephrine was commonly administered with induction in doses of 100-200 micrograms. If additional hemodynamic support was anticipated, proper monitoring and access was established prior to airway management. If additional hemodynamic support is required, norepinephrine, a first-line agent in septic shock, is recommended [12] . Table 2 summarizes pharmacologic considerations for intubating COVID-19 patients.

During laryngoscopy and intubation, COVID-19 patients desaturate very quickly. These patients have little to no reserve even with optimal pre-oxygenation but that must not distract the anesthesiologist from establishing an advanced airway. Also, desaturation commonly persisted immediately after intubation. Early on in the pandemic, practitioners were fooled by the persistent desaturation and convinced to replace the ETT. Rather than removal and replacement, confirmation through visualization from video laryngoscope, end-tidal carbon dioxide along with bilateral chest rise should be utilized to confirm ETT placement. The patient can be bag ventilated for a 3-4 breaths to allow for this. When connecting the ventilator circuit, place the viral filter proximal and ensure the ETT cuff is inflated to avoid aerosolization.

In many circumstances, the anesthesiologist will be required to manage the airway in a cardiac/respiratory arrest. These situations may become chaotic and stressful especially in a COVID patient and efficient securing of the airway and reducing exposure remain critical. It is imperative that the anesthesiologist remain vigilant and calm and quickly survey the room for the necessary equipment. In addition, to recommendations discussed, the anesthesiologist must limit mask ventilation and immediately secure the airway. Most importantly, the code team must cease chest compressions during laryngoscopy and intubation and should only continue once the ETT placement and cuff inflation is confirmed to reduce aerosolization and exposure to the anesthesiologist and any other member of team assisting with the airway. The ventilator should be immediately connected ensuring in-line viral filters.

After completion of the intubation and prior to doffing the PPE, the next steps include discarding and sterilization. Any single use including syringes, stylets, blades, should be discarded prior to exiting the room. Equipment such as the video laryngoscope should be disinfected and sterilized after exiting the room but in a designated area where doffing will occur to avoid viral spread and contamination [15] .

Illness resulting from COVID-19 not uncommonly requires urgent intubation. From a logistical perspective, vigilance is of utmost importance to guarantee proper PPE and protection from the virus. This can be ensured by a buddy system to watch appropriate donning and doffing of PPE. A buddy system can also help to acquire additional medications or equipment and alternate intubations to avoid fatigue.

Because COVID 19 is a novel disease, information will continue to emerge and departmental discussions should continue to update best practices. As we in New York City have encountered a disproportionate number of cases within the United States, we feel uniquely qualified to help disseminate what we have found to be the safest and most efficient ways to take care of these patients. 

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COVID-19) -United States

COVID-19 Infection: Implications for Perioperative and Critical Care Physicians

Precautions for Intubating Patients with COVID-19

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease

Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target

Harmful molecular mechanisms in sepsis

Potential risk of the kidney vulnerable to novel coronavirus 2019 infection

The effects of anesthetic agents on cardiac function

Effects of anaesthesia techniques and drugs on pulmonary function

Concerns of the anesthesiologist: anesthetic induction in severe sepsis or septic shock patients

A Review of Anesthetic Effects on Renal Function: Potential Organ Protection

Effects of etomidate on adrenal suppression: a review of intubated septic patients

Anesthetic Management of Patients with COVID 19 Infections during Emergency Procedures