Clinical trial NCT03198208: Intraoperative Fentanyl Dose on Respiratory Complications
Official title: Effects of Intraoperative Fentanyl Dose on Postoperative Respiratory Complications
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Fentanyl
Opioid Use
Surgery
Respiratory Complication
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2017-06-26
Enrollment: 183396
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with surgeries performed between 01/2007 and 12/2015 at Massachusetts General Hospital and two affiliated community hospitals.

Brief summary: Fentanyl is the most commonly used opioid during anesthesia at Massachusetts General Hospital. Compared to other opioids, e.g. sulfentanil and remifentanil, fentanyl's pharmacokinetic properties are more problematic as the context sensitive half-time increases with duration of fentanyl infusion. This may lead to respiratory complications particularly in patients who receive fentanyl for surgical procedures of long duration. Considering the common use of fentanyl during surgery and its duration of action that is hard to predict during long surgical procedures, we will evaluate the association between intraoperative fentanyl dose and postoperative respiratory complications within 3 days of surgery.

Detailed description: Our team has conducted a series of studies to define the optimal anesthesia plan that minimizes the risk of postoperative respiratory complications. Opioids are almost always used in the perioperative management of patients undergoing surgery during anesthesia. Intraoperatively they are administered to achieve adequate surgical conditions. Opioids are respiratory depressants. They decrease dose-dependently the drive to the respiratory pump muscles and upper airway dilator muscles, which leads to respiratory acidemia and hypercapnia. Fentanyl is the most commonly used opioid during anesthesia at MGH. Compared to other opioids, e.g. sulfentanil and remifentanil, fentanyls pharmacokinetic is more problematic as the context sensitive half-life increases with duration of fentanyl administration. This may lead to respiratory complications. Considering the common use of fentanyl during surgery and its duration of action that is hard to predict during long surgical procedures, we will evaluate the association between intraoperative fentanyl dose and postoperative respiratory complications within 3 days of surgery.

To account for other factors that may affect the incidence of postoperative respiratory complications, we included the following confounder model in all of our analyses:

* Gender
* Age
* BMI (body mass index)
* ASA status classification
* CCI (Charlson Comorbidity Index)
* Inhalational anesthetics as MAC
* Long lasting opioids as IV-morphine milligram equivalent including morphine, hydromorphone, methadone and sufentanil.
* Use of neuraxial anesthesia
* Intraoperative vasopressor dose
* Intraoperative NMBA (neuromuscular blocking agent) dose
* Intraoperative hypotension as number of minutes of an MAP (mean arterial pressure) \<55 mmHG
* Duration of surgery
* Emergency status
* Intraoperative fluids
* PRBC (packed red blood cells) units
* Work RVU \[relative value unit\]
* Surgical service
* Admission type (ambulatory vs inpatient)
* SPORC (Score for Prediction of Postoperative Respiratory Complications)
* SPOSA (Score for Prediction of Obstructive Sleep Apnea)
* Inspiratory O2 - Fraction
* Protective ventilation (defined as PEEP=5 and plateau pressure between 0 and 16)
* Perioperative naloxone use
* Prescription of any of the following opioids within 90 days prior to surgery: oxycodone, codeine, hydrocodone, buprenorphine, butorphanol, opium, hydromorphone, fentanyl, meperidine, morphine, levorphanol, methadone, nalbuphine, tapentadol, oxymorphone, roxicodone, tramadol
* Code status (DNR)

Eligibility criteria: Inclusion Criteria:

* Surgical patients at Massachusetts General Hospital and two affiliated community hospitals
* 18 years of age and older
* Only patients who required general anesthesia with an endotracheal tube for the surgical procedure and were extubated in the operating room at the end of the procedure.

Exclusion Criteria:

* Brain dead patients (ASA greater than 5)

Primary outcomes:
measure: Postoperative respiratory complications
timeFrame: Between the day of surgery and the third day after surgery
Secondary outcomes:
Other outcomes:
measure: Post-extubation desaturation
timeFrame: Immediately after endotracheal extubation at the end of surgery
measure: Non-invasive ventilation
timeFrame: Between the day of surgery and the third day after surgery
measure: ICU admission rate
timeFrame: Between day of surgery and hospital discharge, may be up to one year
measure: Hospital length of stay
timeFrame: Number of days between day of hospital admission and hospital discharge, may be up to one year
measure: Total hospital costs
timeFrame: Between day of hospital admission and hospital discharge, may be up to one year
measure: Wound infection
timeFrame: Between the day of surgery and 30 days after surgery
Locations:
city: Boston
country: United States
facility: The Massachusetts General Hospital
state: Massachusetts
Study officials:
References:
citation: Ruscic KJ, Grabitz SD, Rudolph MI, Eikermann M. Prevention of respiratory complications of the surgical patient: actionable plan for continued process improvement. Curr Opin Anaesthesiol. 2017 Jun;30(3):399-408. doi: 10.1097/ACO.0000000000000465.
citation: Thevathasan T, Shih SL, Safavi KC, Berger DL, Burns SM, Grabitz SD, Glidden RS, Zafonte RD, Eikermann M, Schneider JC. Association between intraoperative non-depolarising neuromuscular blocking agent dose and 30-day readmission after abdominal surgery. Br J Anaesth. 2017 Oct 1;119(4):595-605. doi: 10.1093/bja/aex240.
citation: de Jong MAC, Ladha KS, Vidal Melo MF, Staehr-Rye AK, Bittner EA, Kurth T, Eikermann M. Differential Effects of Intraoperative Positive End-expiratory Pressure (PEEP) on Respiratory Outcome in Major Abdominal Surgery Versus Craniotomy. Ann Surg. 2016 Aug;264(2):362-369. doi: 10.1097/SLA.0000000000001499.
citation: Ladha K, Vidal Melo MF, McLean DJ, Wanderer JP, Grabitz SD, Kurth T, Eikermann M. Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study. BMJ. 2015 Jul 14;351:h3646. doi: 10.1136/bmj.h3646.
citation: Shin CH, Grabitz SD, Timm FP, Mueller N, Chhangani K, Ladha K, Devine S, Kurth T, Eikermann M. Development and validation of a Score for Preoperative Prediction of Obstructive Sleep Apnea (SPOSA) and its perioperative outcomes. BMC Anesthesiol. 2017 May 30;17(1):71. doi: 10.1186/s12871-017-0361-z.
citation: Brueckmann B, Villa-Uribe JL, Bateman BT, Grosse-Sundrup M, Hess DR, Schlett CL, Eikermann M. Development and validation of a score for prediction of postoperative respiratory complications. Anesthesiology. 2013 Jun;118(6):1276-85. doi: 10.1097/ALN.0b013e318293065c.
citation: Friedrich S, Raub D, Teja BJ, Neves SE, Thevathasan T, Houle TT, Eikermann M. Effects of low-dose intraoperative fentanyl on postoperative respiratory complication rate: a pre-specified, retrospective analysis. Br J Anaesth. 2019 Jun;122(6):e180-e188. doi: 10.1016/j.bja.2019.03.017. Epub 2019 Apr 11.