Dexamethasone and Postoperative Delirium
| Status: | Recruiting |
|---|---|
| Conditions: | Cognitive Studies, Hospital, Neurology, Psychiatric |
| Therapuetic Areas: | Neurology, Psychiatry / Psychology, Other |
| Healthy: | No |
| Age Range: | 70 - 100 |
| Updated: | 6/1/2018 |
| Start Date: | April 2014 |
| End Date: | December 2019 |
| Contact: | Glenn S Murphy, MD |
| Email: | dgmurphy2@yahoo.com |
| Phone: | 847-570-2760 |
Postoperative delirium is commonly observed in elderly patients in the postanesthesia care
unit (PACU) and during the first 2-3 days following surgical procedures. This is an important
clinical problem in the geriatric surgical patient; morbidity and mortality rates are
significantly higher in patients who develop delirium. At the present time, the etiology of
delirium has not been precisely defined. However, studies suggest that inflammation related
to the surgical stress response is an important contributing factor in inducing
neuroinflammation and subsequent cognitive dysfunction and delirium. Therefore it is possible
that agents which attenuate perioperative inflammation may reduce the risk of the development
of delirium following surgery. Dexamethasone is a potent corticosteroid that is used by
anesthesiologists primarily as an antiemetic agent. Small doses of dexamethasone have also
been demonstrated to significantly reduce the release of inflammatory markers after surgery.
The anti-inflammatory effects of corticosteroids have the potential to beneficially impact
neuroinflammation and the risk of developing postoperative delirium. The aim of this
randomized, controlled, double-blinded investigation is to determine if dexamethasone,
administered at induction of anesthesia, can decrease the incidence of delirium at the time
of discharge from the PACU and during the first 2 days following surgery.
unit (PACU) and during the first 2-3 days following surgical procedures. This is an important
clinical problem in the geriatric surgical patient; morbidity and mortality rates are
significantly higher in patients who develop delirium. At the present time, the etiology of
delirium has not been precisely defined. However, studies suggest that inflammation related
to the surgical stress response is an important contributing factor in inducing
neuroinflammation and subsequent cognitive dysfunction and delirium. Therefore it is possible
that agents which attenuate perioperative inflammation may reduce the risk of the development
of delirium following surgery. Dexamethasone is a potent corticosteroid that is used by
anesthesiologists primarily as an antiemetic agent. Small doses of dexamethasone have also
been demonstrated to significantly reduce the release of inflammatory markers after surgery.
The anti-inflammatory effects of corticosteroids have the potential to beneficially impact
neuroinflammation and the risk of developing postoperative delirium. The aim of this
randomized, controlled, double-blinded investigation is to determine if dexamethasone,
administered at induction of anesthesia, can decrease the incidence of delirium at the time
of discharge from the PACU and during the first 2 days following surgery.
This study will be a randomized, placebo-controlled, double blind clinical investigation.
Four hundred patients scheduled for surgical procedures under general anesthesia will be
enrolled. Patients will be randomized via a computerized randomization table to one of two
groups; a dexamethasone group (10 mg of dexamethasone in a 5 cc syringe) or a control group
(an equal volume of saline in a 5 cc syringe)). A dose of 10 mg of dexamethasone was
selected, as this reflects a dose that has been demonstrated to attenuate the inflammatory
response to surgery, decrease pain, and improve clinical recovery. This is also within the
dose range commonly used at NorthShore University HealthSystem. The drug/placebo solution
will be prepared by the pharmacy into the syringes. Both solutions are clear and appear
identical. Study syringes will be prepared by the pharmacy, and all clinicians will be
blinded to group assignment. At the induction of anesthesia, the syringe containing either
dexamethasone or saline will be administered. The administration of all other anesthetic
agents will be standardized and reflect the usual practices of anesthesiologists at
NorthShore University HealthSystem.
Monitoring will consist of standard American Society of Anesthesiologists monitors, which
include manual blood pressure measurements, continuous EKG monitoring, pulse oximetry,
capnography and infrared gas analysis. Additional monitoring, such as direct radial artery
pressure measurements, will be at the discretion of the attending anesthesiologist.
Anesthetic induction will consist of propofol 0.5-2.0 mg/kg, fentanyl 50-100 μg, and
rocuronium 0.6 mg/kg. Anesthesia will be maintained with sevoflurane 0.5-3.0%, with the
concentration of inhalational agent adjusted to maintain blood pressure within 20-30% of
baseline values and depth of anesthesia standardized using a BIS monitor (BIS values 40-60).
Additional doses of fentanyl, up to 1-2 µg/kg/hour, can be administered at the discretion of
the anesthesia care provider. Hydromorphone may be provided for postoperative analgesia.
Hypotension (any decrease in mean arterial pressure ≥ 20%) will be treated with a fluid
bolus, phenylephrine, or ephedrine, as clinically indicated. Thirty minutes before the
anticipated conclusion of the surgical procedure, patients will receive ondansetron 4 mg.
Neuromuscular blockade will be reversed with neostigmine and glycopyrrolate.
Patients will be managed according to standard PACU protocols. Nausea and vomiting will be
treated per standard protocols. Any episodes of nausea and vomiting in the PACU will be noted
on a data collection sheet. Pain will be treated with hydromorphone. Pain scores in the PACU,
as well as total doses of hydromorphone will be recorded. Patients will be discharged from
the PACU when standard criteria are met. Study subjects will be discharged either to the
surgical floor or the intensive care unit (ICU). The times to meet discharge criteria and
actually achieve discharge will be recorded. For patients transferred directly to the ICU
from the operating room, nausea, vomiting, pain scores, and analgesic requirements will be
collected over the first 3 hours of recovery. Postoperatively, pain will be controlled with
intravenous doses of hydromorphone. Intravenous analgesia will be provided until patients are
able to resume oral intake, which usually occurs on the first or second postoperative day. At
this time, analgesic management will be transitioned to oral pain medication (typically
hydrocodone 5 mg / acetaminophen 500 mg). Total doses of intravenous and oral pain
medications will be recorded during the hospitalization. Postoperative pain scores will be
assessed at the same time testing for delirium is performed during the postoperative period.
Four hundred patients scheduled for surgical procedures under general anesthesia will be
enrolled. Patients will be randomized via a computerized randomization table to one of two
groups; a dexamethasone group (10 mg of dexamethasone in a 5 cc syringe) or a control group
(an equal volume of saline in a 5 cc syringe)). A dose of 10 mg of dexamethasone was
selected, as this reflects a dose that has been demonstrated to attenuate the inflammatory
response to surgery, decrease pain, and improve clinical recovery. This is also within the
dose range commonly used at NorthShore University HealthSystem. The drug/placebo solution
will be prepared by the pharmacy into the syringes. Both solutions are clear and appear
identical. Study syringes will be prepared by the pharmacy, and all clinicians will be
blinded to group assignment. At the induction of anesthesia, the syringe containing either
dexamethasone or saline will be administered. The administration of all other anesthetic
agents will be standardized and reflect the usual practices of anesthesiologists at
NorthShore University HealthSystem.
Monitoring will consist of standard American Society of Anesthesiologists monitors, which
include manual blood pressure measurements, continuous EKG monitoring, pulse oximetry,
capnography and infrared gas analysis. Additional monitoring, such as direct radial artery
pressure measurements, will be at the discretion of the attending anesthesiologist.
Anesthetic induction will consist of propofol 0.5-2.0 mg/kg, fentanyl 50-100 μg, and
rocuronium 0.6 mg/kg. Anesthesia will be maintained with sevoflurane 0.5-3.0%, with the
concentration of inhalational agent adjusted to maintain blood pressure within 20-30% of
baseline values and depth of anesthesia standardized using a BIS monitor (BIS values 40-60).
Additional doses of fentanyl, up to 1-2 µg/kg/hour, can be administered at the discretion of
the anesthesia care provider. Hydromorphone may be provided for postoperative analgesia.
Hypotension (any decrease in mean arterial pressure ≥ 20%) will be treated with a fluid
bolus, phenylephrine, or ephedrine, as clinically indicated. Thirty minutes before the
anticipated conclusion of the surgical procedure, patients will receive ondansetron 4 mg.
Neuromuscular blockade will be reversed with neostigmine and glycopyrrolate.
Patients will be managed according to standard PACU protocols. Nausea and vomiting will be
treated per standard protocols. Any episodes of nausea and vomiting in the PACU will be noted
on a data collection sheet. Pain will be treated with hydromorphone. Pain scores in the PACU,
as well as total doses of hydromorphone will be recorded. Patients will be discharged from
the PACU when standard criteria are met. Study subjects will be discharged either to the
surgical floor or the intensive care unit (ICU). The times to meet discharge criteria and
actually achieve discharge will be recorded. For patients transferred directly to the ICU
from the operating room, nausea, vomiting, pain scores, and analgesic requirements will be
collected over the first 3 hours of recovery. Postoperatively, pain will be controlled with
intravenous doses of hydromorphone. Intravenous analgesia will be provided until patients are
able to resume oral intake, which usually occurs on the first or second postoperative day. At
this time, analgesic management will be transitioned to oral pain medication (typically
hydrocodone 5 mg / acetaminophen 500 mg). Total doses of intravenous and oral pain
medications will be recorded during the hospitalization. Postoperative pain scores will be
assessed at the same time testing for delirium is performed during the postoperative period.
Inclusion Criteria:
- patients ≥ 70 years of age, undergoing a noncardiac surgical procedure under general
anesthesia, with an anticipated duration of postoperative admission of at least 2
days.
Exclusion Criteria:
- 1) preoperative diagnosis of delirium or dementia; 2) MMSE score of ≤ 20 out of 30 on
preoperative testing (more than mild cognitive impairment) or delirium on preoperative
CAM testing; 3) language barriers that would preclude testing; 4) preoperative steroid
use within 3 days of surgery; or 5) anticipation of postoperative intubation.
We found this trial at
1
site
Evanston, Illinois
Principal Investigator: Glenn S Murphy, MD
Phone: 847-570-2760
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