Delayed sequence intubation with ketamine in 2 critically ill children


Kudos to the authors(Michael Miescier , Rob Bryant & Douglas Nelson) of this published paper for allowing the accepted manuscript to be posted here for open access! (permitted under Elsevier authorship conditions)

Here is link to the published paper on American Journal of emergency medicine.

Below is the accepted full text manuscript :

Delayed sequence intubation with ketamine in 2 critically ill children

Michael J. Miescier, MD, MPH
Division of Pediatric Emergency Medicine, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT
Robert J. Bryant, MD
Emergency Medicine (Clinical), Division of Emergency Medicine, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT
1Tel: +1 801 581 2730; fax: +1 801 585 0603.
Douglas S. Nelson, MD
Division of Pediatric Emergency Medicine, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT
Tel.: +1 801 587 7450; fax: +1 801 587 7455.


Hypoxia is a common complication during the emergent intubation of children. Several approaches can help avoid hypoxia, including semi-upright patient positioning, adequate pre-oxygenation, and nasal cannula apneic oxygenation. Delayed sequence intubation (DSI) is a strategy to facilitate pre-oxygenation when standard efforts using supplemental oxygen are not successful. In DSI, the sedative agent ketamine is administered first to facilitate effective pre-oxygenation, followed by the delayed administration of a neuromuscular blocking agent once adequate pre-oxygenation has been achieved. A recent prospective, observational, multicenter study of adults demonstrated that a DSI strategy using ketamine safely increased oxygenation saturations during pre-oxygenation in adults(17). We present the successful use of ketamine for DSI in two critically ill hypoxic children in shock requiring intubation in the emergency department (ED). To date there have only been two other descriptions of the use of pediatric DSI in the literature, both in normotensive patients.(13,14)

DSI is an intubation strategy that can be safely used in pediatric patients who are not able to be pre-oxygenated for intubation using conventional strategies.

Case 1

11 year old ex-premie with developmental delay who presented with a five day history of fever, congestion, and cough. Temp. 36.5 celcius (C), HR 156 bpm, RR 54, BP 126/86 mmHg, SpO2 decreased from 82% to 65%. He was awake, agitated, hypo-perfused, and in respiratory distress. Labs: pH 7.25, pCO2 60 mmHg, lactate 5.6 mmol/L, and hematocrit 51%.

With NRB mask at 15 liters per minute (lpm), his SpO2 only rose to 75%. With continuous positive airway pressure (CPAP) SpO2 improved to 91%. He became more agitated, grabbing at the mask, and received lorazepam 0.03mg/kg IV. BiPAP was titrated to settings of 18/10cm H2O. After initial improvement, SpO2 worsened again to the low 80’s. Chest x-ray was consistent with viral pneumonia. He received ceftriaxone IV, and a total of 60mL/kg of IV NS with moderate improvement in his perfusion.

To decrease his agitation he was given Ketamine 1mg/kg IV, with improvement, however SpO2 remained 73% on FiO2 100% with bag mask ventilation. Over the next 20 minutes he was given two additional doses of ketamine 1mg/kg IV. His agitation improved and SpO2 rose to 92% with bag-valve-mask ventilation. Nasal cannula oxygen at 15 lpm was applied prior to administration of Rocuronium 1 mg/kg IV. He received atropine 0.02 mg/kg IV before intubation. He was intubated with a 5.5 cuffed endotracheal tube (ETT). SpO2 did not drop during the intubation.

He was extubated after 48 hours, and discharged home on hospital day 5 with a discharge diagnosis of human metapneumovirus and presumed bacterial pneumonia.

Case 2

11 month old previously healthy boy arrived after a two-hour aeromedical transport for small bowel obstruction confirmed on abdominal CT. He had received IV antibiotics and a total of 130mL/kg of NS IV over a 6 hour period for hypotension. BP: 59/42 mmHg, HR 194 bpm, RR 54 rpm, temp. 36.0 C. SpO2 was 78 to 82% on a NRB mask with a poor waveform. He had depressed mental status and clinical evidence of hypoperfusion with diminished femoral and radial pulses. Breath sounds were decreased bilaterally. His abdomen was distended and tender, and a nasogastric tube was draining bile. Lab results included pH 6.89, pCO2 63 mmHg, bicarbonate 12 mmol/L, hemoglobin 3.7 mg/dL, and lactate 8.7 mmol/L. Dopamine infusion was started along with a Normal saline bolus of 20mL/kg IV. Blood pressure improved to 86/66 mmHg but SpO2 remained 73% on 10 lpm NRB mask.

He received atropine 0.2 mg IV and ketamine 2 mg/kg IV. With CPAP SpO2 improved to 85%. Nasal cannula oxygen was applied. He then received Rocuronium 1mg/kg IV and intubation with a 4.0 cuffed ETT with saturations remaining at 85%.

A partial resection of small intestine was performed for malrotation andmidgut volvulus, and he was discharged home on hospital day 43.


Emergency intubation of children is associated with significant risks of hypoxia (29%), and hypotension (16%) (2). Children 24 months and younger are at higher risk for hypoxia (59%) (3). Peri-intubation hypoxia can be mitigated using the dual strategies of effective pre-oxygenation and apneic oxygenation during intubation.(5,6) Standard pre-oxygenation is typically accomplished using a NRB mask alone.

Strategies that have been shown to prolong the safe apnea duration in adult elective anesthesia patients include semi-upright position(7,8), application of continuous positive pressure (CPAP) (9,10), and apneic oxygenation (11).

Some patients may not tolerate pre-oxygenation attempts due to agitation from a variety of etiologies including hypoxia, hypercarbia, central nervous system pathology, intoxication, and psychiatric or behavioral problems. In these cases performing DSI can help a patient tolerate pre-oxygenation (1). DSI is in essence a procedural sedation, where the procedure is pre-oxygenation. (1) Ketamine is the recommended sedative for DSI since it does not suppress respiratory drive or airway reflexes (1,12). Once the patient is pre-oxygenated, a neuromuscular blocking agent is given, and intubation can proceed while the patient continues to receive supplemental nasal cannula oxygen to provide apneic oxygenation. In both of our cases ketamine was used to facilitate the use of non invasive positive pressure ventilation (NIPPV) for pre-oxygenation.

Ketamine has favorable hemodynamic effects that are useful during the intubation of a critically ill child. Ketamine’s net effect is to increase heart rate and increase blood pressure via blockade of reuptake of catecholamines and direct alpha and beta adrenergic effects, despite a direct negative inotropic effect (12). In patients with catecholamine depletion reduced doses of ketamine of 0.5 to 1mg/kg IV is advised (16). In one report two critically ill patients experienced cardiac arrest following the administration of ketamine for intubation. Both patients had received higher doses of ketamine (2 mg/kg and 2.4 mg/kg). The authors postulated that cardiac arrest was due to the direct negative inotropic effects of ketamine (15).

DSI is an appropriate intubation strategy for critically ill pediatric patients who cannot be preoxygenated using traditional strategies of NRB or NIPPV.


(1) Weingart SD. Preoxygenation, reoxygenation, and delayed sequence intubation in the emergency department. J Emerg Med. 2011;40:661-667.

(2) Carroll CL, Spinella PC, Corsi JM, et al. Emergent endotracheal intubations in children: be careful if it’s late when you intubate. Pediatr Crit Care Med.2010;11:343–348.

(3) Rinderknecht AS, Mittiga MR, Meinzen-Derr J, et al. Factors associated with oxyhemoglobin desaturation during rapid sequence intubation in a pediatric emergency department: findings from multivariable analyses of video review data.Acad Emerg Med. 2015;22:431–440.

(4) Heffner AC, Swords DS, Neale MN, et al. Incidence and factors associated with cardiac arrest complicating emergency airway management. Resuscitation.2013;84:1500–1504.

(5) Weingart SD, Levitan RM. Preoxygenation and prevention of desaturation during emergency airway management. Ann Emerg Med. 2012;59:165-175.

(6) Xue FS, Tong SY, Wang XL, et al. Study of the optimal duration of preoxygenation in children. J Clin Anesth. 1995;7:93-96.

(7) Lane S, Saunders D, Schofield, et al. A prospective, randomised controlled trial comparing the efficacy of pre-oxygenation in the 20° head-up vs supine position.Anaesthesia. 2005;60:1064–1067.

(8) Ramkumar V, Umesh G, Phillip FA. Preoxygenation with 20 degrees head-up tilt provides longer duration of non-hypoxic apnea than conventional preoxygenation
in non-obese healthy adults. J Anesth. 2011;25:189–194.

(9) Gander S, Frascarolo P, Suter M, et al. Positive end-expiratory pressure during induction of general anesthesia increases duration of nonhypoxic apnea in morbidly obese patients. Anesth Analg. 2005;100:580-584.

(10) Herriger A, Frascarolo P, Spahn DR, et al. The effect of positive airway pressure during pre-oxygenation and induction of anaesthesia upon duration of non-hypoxic apnoea. Anaesthesia. 2004;59:243-247.

(11) Christodoulou C, Rohald P, Mullen T, et al. Apneic oxygenation via nasal prongs at 10 L/min prevents hypoxemia during tracheal intubation for elective surgery. ERJ 2013;42:Suppl 57 P4923.

(12) Bergman SA. Ketamine: a review of its pharmacology and its use in pediatric anesthesia. Anesth Prog. 1999;46:10-20.

(13) Schneider ED, Weingart S. A case of delayed sequence intubation in a pediatric patient with respiratory syncytial virus. Ann Emerg Med. 2013;62:278–9.

(14) Lollgen RM, Webster P, Lei E. Delayed sequence intubation for management of respiratory failure in a 6-year-old child in
a paediatric emergency department.Emergency Medicine Australasia 2014;26:308–319.

(15) Dewhirst E, Frazier JF, Leder M, et al. Cardiac arrest following ketamine administration for rapid sequence intubation. J Intensive Care Med. 2013;28:375-379.

(16) Stollings JL, Diedrich DA, Oyen LJ, et al. Rapid-sequence intubation: a review of the process and considerations when choosing medications. Annals Pharm.

(17) Weingart SD, Trueger NS, Wong N, Scofi J,Singh N, Rudolph SS. Delayed Sequence Intubation : a prospective observational study. Ann Emerg Med. 2015 Apr;65(4):349-55

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