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The A1 Sedation Package: Better Care for Intubated Patients
You are called to the scene of a 56-year-old male found unresponsive in his garage workshop. Upon examining him you find him minimally responsive to painful stimulus, moaning and groaning. His family tells you he has high blood pressure, diabetes, and a previous MI. His blood glucose is mildly elevated at 156 mg/dL.
After moving the man into the ambulance, you realize he has become completely unresponsive, with slow, snoring respirations. Simple maneuvers do not correct the situation, and you elect to perform rapid-sequence induction (RSI) to protect his airway and ensure adequate ventilation and oxygenation.
Following a period of preoxygenation, you push your sedative and paralytic and place an 8.0 endotracheal tube. You confirm placement with continuous waveform capnography and monitoring vital signs. His vitals following intubation are blood pressure 128/76, heart rate 84 bpm, respiratory rate 16 (by BVM), EtCO2 38 mmHg, and SpO2 97%.
About 15 minutes into your transport, you notice his blood pressure is 190/100 mmHg, and his heart rate has climbed to 124 bpm. What has happened? What interventions might you consider?
Preparing for Postintubation
This isn’t one of those trick questions where you have to pick the best of several good options. In this real-life setting, we need to be thinking about our entire management plan.
Unfortunately many of us fall into the trap of thinking about patient care and clinical interventions as discrete steps, rather than a continuum. This failure to think and prepare for a few minutes for steps down the road can have serious repercussions for our patients.
One of the best examples of this (or worst, if you’re unfortunate enough to be the patient) occurs when our patient needs invasive airway management. When we’re preparing for an emergent intubation, what happens after the tube goes in may not be the first thing on our minds. We can become fixated on the various preparatory tasks essential for a safe intubation. Though that preparation is critical and deserves careful attention, preparation for postintubation care is equally important.
Once the airway is secured, we can find ourselves seduced by the euphoria of successfully completing a complex and difficult task, which may cause us to fail to recognize the need to complete subsequent but equally important tasks. This is a cognitive trap known as success fixation. This is important in the context of airway management because what happens after the intubation is just as important as what happens before and during the procedure.
Endotracheal intubation is not a painless intervention. By way of example, attempt the following: Insert three of your fingers as far into your throat as you can. Now leave them there for the next hour. This is an unpleasant exercise, and good sense dictates you probably shouldn’t attempt it. But this crude approximation of being intubated is not far from what we ask our intubated patients to tolerate.
To facilitate placement of an invasive airway, many EMS systems allow their providers to administer sedative and paralytic medications prior to intubation. An unintended and often unrecognized downstream result is achieving a successfully intubated patient whose sedative has worn off but who is still pharmacologically paralyzed.
Consider this for a moment: Your patient is experiencing pain and has conscious awareness of their surroundings but is paralyzed and powerless to communicate their pain and fear. They can’t move, they can’t scream. They can’t do anything to escape the terror they’re experiencing—and it is true terror. The term for this is anesthesia awareness, and it is estimated to occur in 1 in 1,000 cases of general anesthesia occurring in the operating room, although experts believe the true incidence may be higher due to underreporting. Data regarding the occurrence of anesthesia awareness in the ED is even more limited, although one article describes its occurrence in as many as 50% of ED RSI cases.1,2
Anyone with experience in EMS or emergency medicine has likely seen this scenario at least once: The patient has been successfully intubated, but someone inevitably breaks the postintubation euphoria by wondering, “Why is her blood pressure 240/140 mmHg? Is she having a stroke? Is there some medication we should use to bring it down?”
While astute providers may recognize elevated blood pressure, heart rate, and the presence of tears as signs of patient distress, too often our patients have experienced several minutes or even hours of inadequate sedation and analgesia before these signs are recognized.
Stacking the Deck
RSI—also known as medically assisted airway management (MAAM) and drug-facilitated intubation (DFI)—is frequently employed by paramedics in the prehospital environment to achieve tracheal intubation. With this approach, two and sometimes three types of medication are administered to the patient prior to invasive airway insertion: a sedative/anesthetic, a paralytic, and sometimes an analgesic.
Etomidate remains the most common anesthetic agent used for RSI by EMS; midazolam is also commonly employed. Etomidate provides excellent anesthesia, although its duration of effect is limited to 5–10 minutes. Midazolam can be effective as well, but higher doses are frequently required, and its time of onset makes it less desirable for emergency intubation. The duration of midazolam’s effect is variable and depends on dose and patient-specific responses.
Following induction of anesthesia, a neuromuscular blocking agent, or paralytic, is given to induce paralysis. A critical point in pharmacology awareness and understanding is that paralytic drugs do not provide any sedation or analgesia for the patient.
In the United States, succinylcholine (suxamethonium chloride) and rocuronium bromide are the most commonly used neuromuscular blocking agents.3 Succinylcholine is a depolarizing neuromuscular blocker that induces complete paralysis for 5–10 minutes. Recent research has suggested that succinylcholine has been associated with worse outcomes in several clinical states, such as septic shock and traumatic brain injury. This is thought to be due to the increased oxygen consumption associated with succinylcholine’s depolarizing mechanism of action.
For this reason rocuronium has become increasingly popular for RSI in EMS and the ED.4 As a nondepolarizing neuromuscular blocker, rocuronium avoids many of these issues. It is also the preferred paralytic in pediatric anesthesia. When dosed appropriately its time of onset is similar to succinylcholine’s, but with a much longer duration of action—on the order of 30–45 minutes.
Though paralytic agents such as rocuronium have several benefits over succinylcholine, their longer duration of paralysis sets the stage for the patient to experience anesthesia awareness. The duration of effect of conventional sedatives (e.g., etomidate or propofol) is 5–10 minutes, while the duration of paralysis from rocuronium is 30–45 minutes.
Thus patients may end up trapped in a nightmare of being fully awake, aware, and in pain but also paralyzed. It is heartbreaking that the only physical sign of this torturous state may be the patient’s tears. For EMS teams with long transport times, this is an especially pressing issue.
However, EMS crews in highly urban environments must also be attentive to this dilemma, as even short transport times can easily exceed 5–10 minutes. How can this problem be avoided?
PIASA: Pain First
Postinvasive airway sedation and analgesia (PIASA) is as critical to our patients’ well-being as our careful management of oxygenation and perfusion in the pre- and peri-intubation periods.
In addition to anesthesia awareness, inadequate sedation and analgesia in paralyzed and intubated patients can lead to increased catecholamine release, increased production of lactic acid, and increased metabolic oxygen demands, all of which can contribute to significant morbidity and mortality in patients who are already critically ill.
Until very recently deep sedation was considered the mainstay of postintubation care. Unfortunately this approach fails to recognize that sedation does not equal analgesia. Consequently patients are frequently left heavily sedated but still in pain.
Agitation is a frequent result of this approach, and instead of leading us to administer pain medication, we frequently and mistakenly interpret the agitation as a sign that even more sedatives are needed.5,6
In recent years compelling evidence has suggested that instead of more sedation, our first reach should be for pain medications. Patients who are oversedated have no awareness of their surroundings, which disposes them to delirium, which is linked to increased mortality. This phenomenon has been well demonstrated in a number of clinical studies.7–10
Additionally, several studies have now shown that the use of benzodiazepines such as midazolam or lorazepam is associated with prolonged ventilator time, prolonged length of ICU stay, and increased delirium.11,12 In place of the historical sedative-driven model, we should now be moving toward what Dr. Scott Weingart and others have called “A1 sedation”—for analgesia first, then sedation.13
In this model we should first address the primary problem associated with intubation: pain. We provide aggressive analgesia first, followed by small doses of sedation when necessary.14–16
Pain Management
Treating the pain associated with advanced airway placement can be accomplished in several ways. Regardless of setting, opioid analgesics should be the central component of postintubation care (the exception may be the hypotensive patient; this is addressed further below).
Synthetic opioids such as fentanyl and hydromorphone may be superior to morphine due to lower levels of histamine release and because their onset of action (particularly fentanyl) is rapid.
Hydromorphone may represent the best available choice due to its excellent analgesic properties combined with a modest duration of effect, which avoids the logistical burden of frequently redosing. Opioids should be titrated to patient-reported comfort when possible, or to achieve comfort goals based on a validated scale such as the Richmond Agitation-Sedation Scale (RASS), which categorizes various levels of both agitation and sedation.
Whichever opioid analgesic is chosen, administer the first dose either concurrently with RSI medications or immediately after the airway has been secured. Observe the patient closely and administer repeat doses until adequate analgesia is achieved.
Remember, the initial analgesic dose may not provide adequate pain management. Patients should be closely monitored throughout transport and additional analgesia provided as needed for signs of pain or distress.
Given the need for ongoing analgesia throughout intubation, providers may consider a continuous fentanyl infusion. Data regarding opiate infusions in the ED and EMS are scarce. However, emerging evidence and expert opinion suggest that boluses of opiates may be superior to a continuous infusion. Josh Farkas, MD, illustrates the flaw in the logic behind continuous fentanyl infusions at the PulmCrit blog: Patients in distress may have their fentanyl infusion continuously increased to the point where they are receiving staggering doses of opioids (on the order of 500–3,000 mg oxycodone daily). This may result in opioid-induced hyperalgesia and opioid withdrawal. These data and concepts are derived from ICU populations, so their applicability to EMS and the ED is uncertain.
One advantage of boluses titrated to signs of pain or distress is that pain medication is titrated to the specific needs of the patient, in contrast to the potential unnecessary excess that may occur with a continuous infusion. Given that intubated patients should be closely and continuously observed by EMS and emergency department providers, intermittent boluses of hydromorphone may represent the most optimal course.
For patients without contraindications, 1–2 mg of IV/IO hydromorphone following airway placement is likely to provide adequate analgesia for the next 20–60 minutes. Subsequent doses of 0.5–1 mg every 20–60 minutes can be provided as necessary. Alternatively, an infusion of 0.5–3 mg/hour may also be initiated. Once adequate analgesia has been achieved, additional medication can be added as necessary to provide light sedation if needed.
Into the K-Hole
One agent that has gained popularity for RSI and postintubation care in recent years is ketamine. Ketamine is now approaching etomidate in its frequency of use for EMS and ED RSI, especially for patients in or at risk of shock.
One prehospital study suggested that a fentanyl/ketamine/rocuronium-based RSI package (Group 1) was superior to one based on etomidate and succinylcholine (Group 2).17 In this study intubating conditions were superior in the group that received fentanyl, ketamine, and rocuronium compared to the group that received etomidate and succinylcholine (100% vs. 95%). Additionally, the incidence of dynamic hypertension following RSI was less in Group 2 compared to Group 1. The incidence of hypotension was similar in both groups.
However, despite its increasing popularity and particularly for patients in shock, it must be understood that ketamine is not a panacea. Contrary to popular belief, ketamine is not a hemodynamically neutral agent.
In patients with intact catecholamine reserves, ketamine administration may be hemodynamically neutral and may in fact increase heart rate and blood pressure. However, like any anesthetic agent, ketamine can negatively impact the blood pressure of patients whose endogenous catecholamine reserves are depleted, such as patients in any stage of shock. For these patients, care must be taken to reduce the dose to avoid peri- and postintubation hypotension.
The shock index, which is calculated by dividing the heart rate by the systolic blood pressure, is a useful predictor of occult shock in a variety of conditions.18,19 A prehospital study of RSI demonstrated that for patients with an elevated shock index, the incidence of hypotension was greater following ketamine administration compared to those with a lower shock index.
This study is useful in two ways: First, it illustrates the importance of provider awareness of shock and the potential for shock when performing RSI. Second, it demonstrates that patients in shock or at risk of shock are at high risk for peri- and postintubation hypotension.20
However, other studies have suggested that when dosed appropriately to the hemodynamic parameters specific to each case, ketamine is likely the most hemodynamically stable anesthetic agent currently available.21 By carefully monitoring and observing the hemodynamic status of each patient prior to RSI, the clinician can tailor the dose of ketamine to provide excellent analgesia and anesthesia while minimizing the likelihood of postintubation hypotension. This may explain its increase in popularity for RSI in EMS and the ED.
Following airway placement ketamine can be used to provide both analgesia and sedation. Boluses of 0.5–2 mg/kg can be given as a slow IV push every 15–45 minutes as needed for pain control and sedation, or a continuous infusion at 0.5–4 mg/kg/hour can be used to generate the same effects. Such doses will provide excellent analgesia and near-total dissociation, which may be desirable in EMS and ED settings.
One significant benefit of ketamine is that unlike propofol and benzodiazepines, ketamine possesses potent analgesic properties at low doses and both analgesic and sedative effects at higher doses. However, due to ketamine’s unique sigmoid dose curve, care must be taken to avoid the partial-dissociation zone, often referred to as the “k-hole,” that exists in the middle-dose range of 0.3–0.7 mg/kg for a normotensive patient. Such a dose can produce a frightening state of dysphoria and agitation rather than one of analgesia and sedation.
In comparison to higher doses, which provide both analgesia and dissociation, there is emerging data that suggests that a low-dose ketamine infusion (0.1–0.3 mg/kg/hr) can be provide ongoing analgesia without significant sedation.22 In this scheme intermittent opioid boluses are used to control breakthrough pain. This strategy may provide excellent analgesia while reducing overall opioid needs.23
Bringing It All Together
It is difficult to imagine a scenario more terrifying than being awake and aware while fully paralyzed. Each time we perform RSI, we must be conscious of this possibility and do everything we can to ensure our patients are not subjected to it. Recognizing that intubation is an inherently painful procedure and the pain will continue as long as an advanced airway is in place, we can instead utilize an “A1 sedation” package, with analgesia first and foremost.
We can use boluses of opioids titrated to the needs of the patient to provide adequate analgesia while minimizing the risks of overmedicating with a continuous infusion. We can recognize that deep sedation leads to increased delirium and mortality and endeavor to use only minimal sedation to maintain patient comfort.
Sidebar: What About Children?
The question of how to approach pediatric patients plagues EMS and, indeed, all of emergency medicine. Should we treat children as little adults? Thankfully, when it comes to RSI and PIASA, the strategies outlined here can be applied to pediatric and adult patients alike. There is evidence that pediatric patients’ pain is often undertreated, which makes awareness of and adherence to these principles even more essential when treating children.24,25
Postintubation care packages for pediatrics should mirror those of adults: Adequate pain management is essential, followed by sedation as needed. Opiates and conventional sedatives have a proven track record of safety. Ketamine has also been shown to be safe and effective in the pediatric population, both for RSI and PIASA.
References
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2. Pandit JJ, Andrade J, Bogod DG, et al. 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: summary of main findings and risk factors. Br J Anaesth, 2014 Oct; 113(4): 549–59.
3. Sagarin MJ, Barton ED, Chng YM, Walls RM; National Emergency Airway Registry Investigators. Airway management by US and Canadian emergency medicine residents: a multicenter analysis of more than 6,000 endotracheal intubation attempts. Ann Emerg Med, 2005 Oct; 46(4): 328–36.
4. Brown CA 3rd, Bair AE, Pallin DJ, Walls RM; NEAR III Investigators. Techniques, success, and adverse events of emergency department adult intubations. Ann Emerg Med, 2015 Apr; 65(4): 363–70.
5. Weingart S. EMCrit Podcast 21—A Bad Sedation Package Leaves Your Patient Trapped in a Nightmare. EMCrit RACC, https://emcrit.org/racc/post-intubation-sedation/.
6. Weingart S. Pain and Terror as Effective Pressors. EMCrit RACC, https://emcrit.org/racc/pain-terror-pressor/.
7. Shehabi Y, Bellomo R, Reade MC, et al.; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med, 2012 Oct 15; 186(8): 724–31.
8. Pandharipande PP, Girard TD, Jackson JC, et al.; for the BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. New Engl J Med, 2013 Oct 3; 369: 1,306–16.
9. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA, 2004 Apr 14; 291(14): 1,753–62.
10. Balzer F, Weiß B, Kumpf O, et al. Early deep sedation is associated with decreased in-hospital and two-year follow-up survival. Crit Care, 2015 Apr 28; 19: 197.
11. Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomized trial. Lancet, 2010 Feb 6; 375(9,713): 475–80.
12. Fraser GL, Devlin JW, Worby CP, et al. Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials. Crit Care Med, 2013 Sep; 41(9 Suppl 1): S30–8.
13. Weingart S. Podcast 115—A New Paradigm for Post-Intubation Pain, Agitation, and Delirium (PAD). EMCrit RACC, https://emcrit.org/racc/post-intubation-sedation-2014/.
14. Stephens RJ, Ablordeppey E, Drewry AM, et al. Analgosedation practices and the impact of sedation depth on clinical outcomes among patients requiring mechanical ventilation in the ED: a cohort study. Chest, 2017 Nov; 152(5): 963–71.
15. Barr J, Fraser GL, Puntillo K, et al.; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med, 2013 Jan; 41(1): 263–306.
16. Vincent JL, Shehabi Y, Walsh TS, et al. Comfort and patient-centred care without excessive sedation: the eCASH concept. Intensive Care Med, 2016 Jun; 42(6): 962–71.
17. Lyon RM, Perkins ZB, Chatterjee D, et al.; Kent, Surrey & Sussex Air Ambulance Trust. Crit Care, 2015 Apr 1; 19: 134.
18. Rady MY, Smithline HA, Blake H, Nowak R, Rivers E. A comparison of the shock index and conventional vital signs to identify acute, critical illness in the emergency department. Ann Emerg Med, 1994 Oct; 24(4): 685–90.
19. Cannon CM, Braxton CC, Kling-Smith M, et al. Utility of the shock index in predicting mortality in traumatically injured patients. J Trauma, 2009 Dec; 67(6): 1,426–30.
20. Miller M, Kruit N, Heldreich C, et al. Hemodynamic response after rapid sequence induction with ketamine in out-of-hospital patients at risk of shock as defined by the shock index. Ann Emerg Med, 2016 Aug; 68(2): 181–8.
21. White PF. Comparative evaluation of intravenous agents for rapid sequence induction—thiopental, ketamine, and midazolam. Anesthesiology, 1982 Oct; 57(4): 279–84.
22. Jouguelet-Lacoste J, La Colla L, Schilling D, Chelly JE. The use of intravenous infusion or single dose of low-dose ketamine for postoperative analgesia: a review of the current literature. Pain Med, 2015 Feb; 16(2): 383–403.
23. Joly V, Richebe P, Guignard B, et al. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology, 2005 Jul; 103(1): 147–55.
24. Alexander J, Manno M. Underuse of analgesia in very young pediatric patients with isolated painful injuries. Ann Emerg Med, 2003 May; 41(5): 617–22.
25. Williams DM, Rindal KE, Cushman JT, Shah MN. Barriers to and enablers for prehospital analgesia for pediatric patients. Prehosp Emerg Care, 2012 Oct–Dec; 16(4): 519–26.
Peter Antevy, MD, is a PEM physician and EMS medical director, and founder and CEO of Pediatric Emergency Standards. He is a featured speaker at EMS World Expo, to be held Oct. 29–Nov. 2 in Nashville, Tenn.
John W. Lyng, MD, FAEMS, FACEP, NRP, is medical director for North Memorial Health Ambulance and Air Care. He is board-certified in both emergency medicine and EMS and is a nationally registered EMT-Paramedic. He is past chair of the NAEMSP Standards and Clinical Practices Committee and has served on the NAEMSP board of directors.
Michael C. Perlmutter, BA, NRP, is a medical student at the University of Minnesota Medical School in Minneapolis. Following paramedic school, he joined North Memorial Health Ambulance and Air Care, where he has worked on the ground and in the air as a critical care and flight paramedic for the last seven years. During this time he served as a field training officer and contributed to protocol development, education, and training initiatives.
