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Table of Contents
SYMPOSIUM: CRITICAL AIRWAY MANAGEMENT
Year : 2014  |  Volume : 4  |  Issue : 1  |  Page : 42-49

Rapid-sequence intubation and cricoid pressure


Department of Anesthesiology and Pain Medicine, Harborview Medical Center, University of Washington School of Medicine, Seattle, Washington, USA

Date of Web Publication3-Mar-2014

Correspondence Address:
Ramesh Ramaiah
Department of Anesthesiology and Pain Medicine, University of Washington, Harborview Medical Center, Box 359724, 325 Ninth Avenue, Seattle,
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2229-5151.128012

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   Abstract 

Airway management is the most important clinical skill for anesthesiologist, emergency physician, and other providers who are involved in oxygenation and ventilation of the lungs. Rapid-sequence intubation is the preferred method to secure airway in patients who are at risk for aspiration because it results in rapid unconsciousness (induction) and neuromuscular blockade (paralysis). Application of cricoid pressure (CP) for patients undergoing rapid-sequence intubation is controversial. Multiple specialty societies have recommended that CP is not effective in preventing aspiration; rather it may worsen laryngoscopic view and impair bag-valve mask ventilation. Some experts think that CP should be applied in trauma and patients at risk for aspiration; however CP, if necessary, should be altered or removed to facilitate intubation.

Keywords: Aspiration, cricoid pressure, rapid-sequence intubation


How to cite this article:
Stewart JC, Bhananker S, Ramaiah R. Rapid-sequence intubation and cricoid pressure. Int J Crit Illn Inj Sci 2014;4:42-9

How to cite this URL:
Stewart JC, Bhananker S, Ramaiah R. Rapid-sequence intubation and cricoid pressure. Int J Crit Illn Inj Sci [serial online] 2014 [cited 2023 Mar 23];4:42-9. Available from: https://www.ijciis.org/text.asp?2014/4/1/42/128012


   Introduction Top


Among the many clinical skills devoted to the airway management both in the operating room (OR) and out of OR, ability to provide a safe and efficient Rapid Sequence Intubation (RSI) is arguably one of the most widely utilized and beneficial when clinically indicated.

Although, the majority of the published data regarding RSI refer to pre-hospital and emergency room induction/intubation, it can be used to guide practice in various healthcare settings. In a multicenter longitudinal study of 8,937 emergency department (ED) intubations from 1997-2002, Walls et al., reported RSI was the initial method chosen in 6,138 of 8,937 intubations (69%) and in 84% of all encounters that involved any intubation medication. [1] Similarly, during a 58 month prospective observational study of physicians performing more than 6,000 intubations at 31 university-affiliated EDs in three nations, Sagarin et al., noted that RSI was used in 78% of initial attempts and resulted in 85-91% success rate of tracheal intubation overall. [2] This trend has also been shown in the pediatric population. The same authors also showed that RSI is the method of choice for the majority of pediatric emergency intubations (81%), and was associated with a high success rate (78%) and a low rate of serious adverse events (1%). [3] Furthermore, RSI has been cited as the most common method used to secure the airway in intensive care unit (ICU) patients by Schwartz et al., [4] indicating the importance of this technique outside of the ED and OR.


   Rapid Sequence Intubation at a Glance Top


In clinical practice, it is generally understood that RSI is used when tracheal intubation must be performed in a patient who is suspected of having a full stomach or is at risk for pulmonary aspiration of gastric contents. The procedure involves three objectives:

  • Preventing hypoxia during the induction-intubation sequence;
  • Minimizing the time between induction and tracheal intubation, when the airway is unprotected by the patient's reflexes or by the cuffed tracheal tube;
  • Applying measures to decrease the chances of pulmonary aspiration of gastric contents.


The first objectives is routinely accomplished by pre-oxygenation, typically 100% oxygen for 3-5 min before induction of anesthesia, allowing the patient to sustain apnea for a period of 5-8 min without hypoxia. [5] The second objective involves minimization of the induction-intubation interval, suggesting that a fast-acting hypnotic agent should be administered along with a rapid onset neuromuscular blocking agent. Finally, measures to decrease the chance of aspiration include applying cricoid pressure (CP), refraining from positive pressure ventilation before tracheal intubation is accomplished, and waiting until neuromuscular blockade is complete to perform laryngoscopy and tracheal intubation [Table 1].
Table 1: Suggested steps for rapid sequence induction

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With RSI being such an integral skill in the management of the airway, guidelines and/or at minimum a consensus as to the proper way to conduct each step of the technique in appropriate situations would be beneficial. As a basis for discussion, it has been suggested that the algorithm of RSI consist of six primary steps: Pre-oxygenation, premedication, induction and muscle relaxation, intubation, primary and secondary confirmation, and post-intubation patient management. [6] Even in the event that a classic RSI is not indicated, modifications to the accepted standards of care are frequently utilized. In a survey of current practice in the US, Rhenfield and associates established three defining features of a modified RSI: Oxygen administration before induction; the use of CP; and an attempt to ventilate the patient's lungs before securing the airway. [7] Studies focusing on the inherent strengths and weaknesses in each step of the algorithm are a recurrent topic in the scientific literature.

Pre-oxygenation has been associated with atelectasis, [5] however, this is a minor problem considering the added protection afforded by prolonging apnea duration secondary to increase in oxygen content in the lungs. Application of CP has been heavily criticized, [8] and positive pressure ventilation has been advocated by some. In addition, there is uncertainty regarding which patients should be considered as having a full stomach and who should undergo RSI. Furthermore, the overall effectiveness of the whole procedure in preventing aspiration of gastric contents has not been evaluated. However, the approach is logical and widely applied.


   Standards and Variations of RSI Application Top


The patient presumed to have a full stomach and requiring emergency surgery often has physiological alterations that are likely to modify the effect of all intravenous (IV) drugs, including neuromuscular blocking agents. Rapid onset of action of neuromuscular blocking agents depends on administration of an appropriate dose, leading to a sufficient plasma concentration and rapid delivery to neuromuscular junctions leading to the production of adequate intubating conditions. Decrease in cardiac output secondary to underlying pathology leads to an increase in peak plasma concentrations as the drug is diluted in a smaller volume. [9] However, a decrease in cardiac output is also associated with a longer onset time. [9]

Safe induction of anesthesia can be accomplished with a variety of medications, however, depending on the clinical scenario encountered; some agents may be more appropriate than others. In a retrospective case-review analysis of RSIs for appendectomies in Canada, Istvan et al., found that opioids, propofol, and neuromuscular blocking agents were given in 98%, 98%, and 99% of patients, respectively. Succinylcholine use was common (80%), with 96% of these patients receiving rocuronium for precurarization. [10]

With the introduction of propofol as a hypnotic agent and the rapidly acting opioid drugs such as alfentanil and remifentanil, the need for neuromuscular blocking agents for intubation has been questioned. However, the quality of intubating conditions is less predictable and tracheal intubation becomes frequently difficult or in some patients impossible, if neuromuscular blocking agents are omitted. In elective intubations, heavy doses of alfentanil (60 μg/kg) or remifentanil (4 μg/kg) are required to produce intubating conditions similar to succinylcholine. [11] These doses are associated with hypotension, and logic dictates that the occurrence of such hypotensive episodes is likely to be exaggerated in emergency patients. Intubation was impossible in 20% of patients who received alfentanil, 30 μg/kg or less, or remifentanil, 3 μg/kg or less. [11] The need for neuromuscular blocking agents seems obvious when one considers the results obtained by emergency physicians. A review of four studies indicated that failure to intubate occurred in 0-1.3% in patients in whom RSI with muscle paralysis was applied compared with 8.6-28% when intubation was performed under sedation only. [12] Three attempts were required in 2-3% of paralyzed patients compared with a 10.7-24% incidence with sedation only. Intense neuromuscular blockade can increase the chance of success at tracheal intubation along with reduced morbidity because aspiration of gastric contents is less likely with profound neuromuscular blockade. [13] Also, the incidence of laryngeal injuries is less if intubating conditions are excellent, and this situation is more frequent if neuromuscular blocking agents are used. [14]

Despite the more general alterations in pharmacodynamics caused by patient pathology, the specific choice of neuromuscular blocking agents used in RSI must also be considered carefully. With the objective to reduce the induction to intubation interval as much as possible, the advantage of a short-onset drug like succinylcholine is obvious choice, yet a short duration of action is also of great value as the apneic interval may often be shorter than the time to onset of hypoxia. An average, non-obese, pre-oxygenated adult may sustain 7-8 min of apnea without becoming hypoxic. [5] The duration of action of succinylcholine 1 mg/kg at the adductor pollicis is slightly longer, 8-12 min, but the diaphragm recovers before the peripheral muscle. At least three studies have tried to tackle this problem. In a small number of volunteers, Heier et al., found that 25% of subjects had oxygen saturation below 80% after a thiopental succinylcholine sequence, whereas the remaining 75% started breathing before onset of desaturation. [15] Hayes et al., reported an 11% incidence of hypoxia in a larger subset of patients, and Naguib et al., noted that 85% of subjects had hypoxia before they started breathing again. [16],[17] Interestingly, the time to resumption of diaphragmatic movements was the same in all three studies cited, 4-5 min, and there was a greater incidence of desaturation in subjects with larger body mass index (BMI). Thus, we can conclude that succinylcholine 1 mg/kg does not allow return of spontaneous respirations before the onset of hypoxia in all patients, as the mean duration of apnea was 4-5 min, but it was reported as long as 9 min in some individuals. Also, the variability in the effectiveness of pre-oxygenation may be more important than variability of succinylcholine effect itself. For example, the quantity of oxygen that can be stored in lungs and body stores is reduced in obese subjects, and increased oxygen consumption, as may occur in trauma and sepsis, is likely to reduce the already brief period of normoxia.

While the need for muscle relaxants for RSI has been demonstrated, there are potential detrimental effects as well. The most deadly instance of such effects is a 'cannot ventilate, cannot intubate' situation. Succinylcholine has been the drug of choice for rapid sequence induction for many years due to its rapid onset, however due to its depolarizing effects and wide range of adverse effects, other drugs have been sought to replace it. Although the short duration of action of succinylcholine offers some kind of protection against the inability to intubate and ventilate, this is not the case with all nondepolarizing agents. Some authors advocate rocuronium as a replacement, with onset nearly as fast as succinylcholine, fewer adverse events. At 1.2 mg/kg, onset of paralysis with rocuronium is less than 1 min [18] but recovery of T1, (minimal level of paralysis needed for reversal of paralysis with neostigmine) can be greater than 40 min. [19] While the ability to recover from succinylcholine in time to begin spontaneous respirations in a 'cannot intubate, cannot ventilate' situation is theoretically possible, return of spontaneous respiration is not possible if rocuronium is used in such situations. Sugammadex, a novel drug for reversal of rocuronium, may solve this problem in patients where the clinical scenario is 'cannot intubate, cannot ventilate' by returning patient to spontaneous ventilation, yet it is not Food and Drug Association (FDA) approved in the US following reports of adverse reactions. [20] Some of the commonly used hypnotics and muscle relaxants used for RSI are listed in [Table 2].
Table 2: Commonly used agents for RSI

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When an adequate dose is administered and if intubation takes place at the appropriate time, intubating conditions are just as good with non-depolarizing muscle relaxants as with succinylcholine. [21] The major difference is the time taken to achieve this. Non-depolarizing drugs, in doses approximating 2 × ED95, will produce neuromuscular blockade in approximately 2-3 min, whereas succinylcholine will achieve the same result in 1 min. However, many studies have shown that a dose of 0.6 mg/kg of rocuronium produces poorer intubating conditions than succinylcholine, and that the dose has to be increased to 1.2 mg/kg to match the effectiveness of succinylcholine. [22]


   Focus on Cricoid Pressure Top


A 2001 survey by Morris and Cook suggests that even though many practitioners do not follow best practice when performing a RSI, several steps in the algorithm were consistently maintained. [23] Of the physicians surveyed, all respondents utilized pre-oxygenation, and although CP was used universally, the practice of its application varied widely. [23] The observation regarding the inconsistency of CP application was again noted in a similar survey conducted in 2012 by Guirro et al., where they found that all anesthesiologists administered pre-oxygenation and applied CP, yet most did not know the correct pressure to be applied on the cricoid cartilage. [24]

CP relating to intubation was described by Sellick in 1961. Using a cadaver, he found that applying backward pressure to the cricoid cartilage against the cervical vertebrae could occlude the upper esophagus and prevent regurgitation of fluid into the pharynx. Sellick then tried the same maneuver during anesthesia induction in 26 patients, who are at increased risk for aspiration. None of the patients experienced regurgitation or vomiting when the pressure was applied, and three patients had immediate reflux into the pharynx upon release of the pressure after tracheal intubation. [25] Sellick's maneuver (CP) gained wide acceptance and was incorporated later as an essential component of RSI. Since then, CP has been considered standard of care during anesthesia induction for patients at high risk of aspiration. However, the evidence, application and validation for CP are much more inconsistent and heavily debated both in clinical practice and the scientific literature. Many practitioners believe in its effectiveness in preventing pulmonary aspiration, whereas others believe it should be abandoned because of the lack of scientific evidence of benefit and possible complications. [11],[26]


   Why Cricoid Pressure? Top


Aspiration pneumonitis (Mendelson's syndrome) is universally accepted as a complication of general anesthesia, as the resultant loss of consciousness and consequent diminished protective airway reflexes ultimately places the patient at risk until their airway is secured. [27],[28] The use of CP was first described by Monro in 1774 as a method for reducing gastric insufflation in near-drowned victims, and as noted above, later addressed by Sellick in 1961 to prevent aspiration of gastric contents during intubation. Unfortunately, however, as many other practitioners have noted, Sellick's original article was lacking in specifics regarding the application of CP, and there have been no RCTs conducted to date which accurately evaluate the validity of his recommendation. Butler and Sen evaluated the current literature regarding the use of CP to prevent aspiration and concluded that there is little evidence to support that CP reduces the incidence of aspiration during an RSI. [13] Furthermore, Neilipovitz and Crosby conducted a search of 52 trials evaluating CP used outside of the context of an RSI, and concluded that the decision to use CP can neither be supported nor discouraged on the basis of quality of evidence. [25] In a 2009 study Fenton and Reynolds found no evidence for a protective effect of CP in preventing regurgitation or death among African parturients. They suggest that preoperative gastric emptying may be a more effective measure to prevent aspiration of gastric contents. [29]

It can be argued that it is the lack of discouraging evidence that makes it difficult to conduct a RCT in today's clinical setting. The application of CP has become so engrained in clinical practice that any Institutional Review Board would be hard pressed to approve the withholding of the technique in a clinical trial. In addition, with a frequency of aspiration of approximately 0.15% in adults, a randomized trial to reduce the incidence of aspiration by 50% would require a sample size of approximately 25,000 patients in each group. [30] However, even should we take the application of CP to be the gold standard in RSI, the notion that aspiration may occur despite the application of CP cannot be overlooked. [30] The technique in itself may have an inherent fixed failure rate even when applied correctly, yet similar failures may occur if CP is applied incorrectly, either in the wrong anatomic position or with less force than required to occlude the esophagus/cricoid pressure unit (CPU), or is released prematurely allowing gastric contents to enter the oropharynx. [30] Therefore, the starting point for improving the efficiency and safety of CP seems to be better teaching and training. [31]


   Laryngeal Anatomy and CP Application Top


The larynx is a cartilaginous skeleton held together by ligaments and muscle [Figure 1]. At the base of the tongue, the epiglottis functionally separates the oropharynx from the laryngopharynx and prevents aspiration by covering the glottis during swallowing. [32]
Figure 1: Anatomy of larynx

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In regards to airway management and the prevention of aspiration as it relates to CP, the anatomical landmarks that we should focus on to identify the physical justification for CP surround the esophagus, cricoid cartilage, and trachea as well as their supporting structures. The cricoid cartilage is the only upper airway cartilaginous structure that is a complete ring. The esophagus begins at the lower portion of the cricoid cartilage; thus pressure anteriorly will compress the esophagus against the anterior vertebral body of the sixth cervical vertebra. [12] In 2001, Schmalfuss et al., sought to establish the normal variations of the post-cricoid portion of the hypopharynx, esophageal verge, and cervical esophagus, as seen on computed tomography (CT) and magnetic resonance imaging (MRI), and showed the esophagus to begin approximately one centimeter distal to the lower level of the cricoid ring. [33] In a follow-up study at the same institution, Rice et al., used MRI to verify that the alimentary canal at the level of the cricoid ring is the post-cricoid hypopharynx and not the esophagus. [34] They continue to note that this anatomic structure is fixed to the cricoid ring by a series of ligaments and muscles described above, and refer to this structure as the CPU. [35]

While evaluating sonographic visualization of empty esophagi to confirm endotracheal tube placement in children and young adults, Tsung observed that the esophagus was visualized lateral to the trachea in all subjects when cricoid pressure was applied using a linear ultrasound transducer. [36] Furthermore, Smith et al., reviewed 51 cervical CT scans of normal subjects and found that the esophagus was displaced laterally, not aligned with the cricoid cartilage in 49% of subjects. [37] The authors then performed a prospective magnetic resonance imaging study to evaluate subjects before and after application of CP. They found lateral displacement in 52.6% of the subjects without CP and 90.5% with CP. The application of CP actually shifted the esophagus to the left in 68.4% of subjects and to the right in 21.1%. Airway compression was demonstrated in 81% of subjects as a result of CP. [37],[38]

With the knowledge that airway management is a kinetically fluid skill, Benkhadra et al., sought to evaluate the displacement of the cricoid cartilage relative to the cervical esophagus during flexion and extension movements of the head. They were able to provide evidence that the esophagus is clearly displaced with regard to the cricoid cartilage, however the extension position of the head produces more displacement of the esophagus, all while preserving the containment of CP in relation to the thickness of the esophageal wall. [39]

However, with the application of cricoid pressure, the compression of the fixed CPU results in consistent occlusion of the alimentary tract at the level of the cricoid ring. The anatomy allows for occlusion of the post-cricoid hypopharynx, regardless of whether the more distally originating esophagus lies in the midline or lateral to it. [34]


   Teaching CP Application Top


In a guide for ED nurses regarding RSI, Armstrong et al., explain that CP is applied from the moment the patient loses consciousness, and remains in place until the endotracheal tube has been inserted in the trachea, cuff inflated, position verified clinically, and end tidal CO 2 monitoring commenced. [40] In 2009, Nafiu et al., set out to assess the theoretic knowledge of ED personnel about CP at the University of Michigan, Ann Arbor, a major academic teaching institution. The survey, which included providers across multiple disciplines and training levels, found that many of the respondents knew the anatomic structure to which CP is applied, however, nearly 30% of respondents thought that CP was applied to both the cricoid and thyroid cartilage. In addition, many of the participants in this survey either were unsure of the recommended amount of cricoid force to be applied or quoted values that were too low, and the majority of respondents rated their training in CP application as either poor or nonexistent. [41]

Brisson and Brisson conducted an observational study showing the great variability in the application of CP, identifying 10 different techniques in 32 observations, noting that misapplication does occur with possible patient harm. They recommend using the three-finger CP technique as originally described by Sellick [Figure 2] and thought that this technique is effective, easy to teach, and safely keeps the fingers in the midline of the cricoid cartilage. [42] It is evident that the educational approach to CP requires some modernization. Estimating and becoming proficient at applying the correct amount of pressure to the cricoid cartilage is a skill in and of itself. It is suggested that 10 Newton's (N) of CP be applied just prior to loss of consciousness, increasing to approximately 30 N force at the onset of anesthesia. [43] The recommended force to prevent gastric reflux is between 30 and 40 N, equivalent to 3-4 kg, but force greater than 20 N can cause pain and retching in awake patients, and a force of 40 N can distort the larynx and complicate intubation. [12] With this knowledge in hand, how are we ensuring that the correct pressure is being applied? Kopka and Crawford suggest a simple biofeedback trainer may be useful in ensuring safe and reliable CP application during RSI, as they were able to show a 48% improvement in the number of trainees able to apply correct awake cricoid force, and a 72% improvement in the number of subjects able to apply correct asleep cricoid force. [44] Flucker et al., also experienced success using a simple 50-millilitre syringe as an inexpensive training aid in the application of CP. Their training lead to a significant improvement in accurate CP application which was maintained for 1 week for both 20 N and 40 N, however, the accuracy of the skill was lost after 1 months time when not routinely evaluated. [45] Just as any other procedural skill in medicine, practitioners must develop the appropriate muscle memory to be able to consistently perform the maneuver, which appears to require frequent evaluation and repetition.
Figure 2: Application of cricoid pressure

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   Cricoid Pressure Risks and Pitfalls Top


Although the application of CP may be a learnable skill, the decision to utilize the technique still remains in the hands of the individual practitioner, and despite the benefits that it may provide, one cannot overlook the potential risks that exist. There are several potential complications to the application of CP, including but not limited to cricoid cartilage fracture, airway obstruction, esophageal rupture in situations of rapid increase in gastric pressure (i.e., vomiting) and even the potential for cervical spine or laryngeal trauma when significant manipulation of the head occurs. [46-50] However, there are many other factors that must be considered as well. CP has been shown to prolong the duration of fiber optic intubation in select patient with mallampati grade airways I-II. [51] Extreme opponents claim that even when correctly applied, CP may actually increase the risk of aspiration, and as noted above, premature application may lead to retching and vomiting. CP was also found to decrease the lower esophageal sphincter (LES) tone from 24 mm Hg to 15 mm Hg when a force of 20 N was applied, and the LES tone further decreased to 12 mm Hg when the force was increased to 40 N, thus decreasing the physiologic barrier to gastric content regurgitation. In addition, even when applied correctly, Boet et al., found that effective application of CP by an experienced operator frequently resulted in lateral deviation of the esophagus and incomplete occlusion of esophageal lumen. [52] The necessity of esophageal occlusion remains debatable however, as discussed earlier in reference to the CPU, it appears as though the position of the esophagus is irrelevant for the success of CP in preventing regurgitation, because the pressure occludes the hypopharynx. [34]


   CP and the Law Top


So with all of the controversy and disagreement surrounding CP, in addition to the lack of evidence supporting or dismissing its proposed benefit, why do we continue to insist on its application on a daily basis? Perhaps, we can shed some light on this question by examining recent accounts of legal action noted in the literature. Cook et al., analyzed claims notified to the National Health Service (NHS) Litigation Authority in England between 1995 and 2007 filed under anesthesia to explore patterns of injury and cost related to airway or respiratory events. The total cost of (non-dental) airway claims was 4.9 million pounds (84% closed, median cost 30,000 pounds) and accounted for 12% of anesthesia-related claims, 53% of deaths, 27% of cost and 10 of the 50 most expensive claims in the dataset, frequently describing events at induction of anesthesia. [53] Furthermore, a retrospective study evaluating malpractice claims at a university hospital in Paris found that out of the 789 claims resulting from surgical activity over a 15-year-period, 41 were directly anesthesia-related, and many of the most frequent problems included the consequences of difficult intubation or aspiration of stomach contents. [54] Expanding on the specific application of CP, a judge in the United Kingdom did rule against an anesthesiologist for failing to apply CP in a patient with an irreducible hernia who had regurgitated and aspirated. The judge argued that we cannot assert "that cricoid pressure is not effective until these trials (RCTs) have been performed, especially as it is an integral part of an anesthetic technique that has been associated with a reduced maternal death rate from aspiration since the 1960s." [55] Thus, regardless of one's approval or disapproval of CP, it is possible that we have necessitated its application simply by the fact that we persistently perform the maneuver, and that it can be classified as "an integral part of an anesthetic technique" by those assessing the legal ramifications of its use, or lack there of.


   Conclusion Top


RSI has proven to be, and will continue to remain an important tool available to the clinical practitioner for induction of anesthesia in applicable situations. The development of new drugs and the acceptance/validation of those less widely utilized will continue to advance the efficacy of the technique and ensure that the excellent level of safety RSI has come to provide does not falter. However, with the ever growing medical complexity of the patient population, standards and algorithms can never completely take the place of an actively vigilant provider, and must continue to be viewed as a guide for best practice.

In the matter of CP, we have not made any significant advancement in the immediate past to irrevocably answer the question as to whether or not the potential benefits of CP outweigh the potential risks such that every patient undergoing RSI should have CP applied. Yet, the more pressing issue may be, is this question even approachable? Perhaps, Leman sums up the heart of the matter in his 2009 review of CP, noting that "we have become far too myopic in focusing more on the documentation that cricoid pressure was applied during induction of anesthesia than on: Investigating the validity of the notion that CP prevents passive regurgitation; focusing on teaching the proper application of CP; focusing on which patients require CP; and focusing on the risk of aspiration during maintenance and emergence from anesthesia." [30] It is important to remember however, that with the ever growing medical complexity of the patient population, standards and algorithms can never completely take the place of an actively vigilant provider, and must continue to be viewed as a guideline for best practice.

 
   References Top

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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]


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