Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06160219 |
| Other study ID # |
FMASU R46/2019 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
August 28, 2019 |
| Est. completion date |
November 27, 2023 |
Study information
| Verified date |
June 2024 |
| Source |
Ain Shams University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Several studies have described the use of alternative drugs as methylene blue (MB) (3) other
than the standard limited options of the use of vasopressors and systemic corticosteroids (4)
especially in the face of increasing incidence of vasoplegic syndrome. Hydroxycobolamin (HCO)
has been used for treating cyanide poisoning for more than 40 years. Persistant and
significant hypertension occurred as a result of the ability of (HCO) to bind nitric oxide
(NO) to form nitrocobalamin.
In this prospective randomized controlled trial, we hypothesized that the prophylactic use of
HCO in high risk patients after CPB may decrease the incidence of vasoplegia.
Description:
Patients and methods
This randomized placebo-controlled single -center study will be conducted in Ain Shams
University Hospital from May 2019 till October 2022. Patients undergoing Cardiopulmonary
bypass grafting (CABG) and/or valve surgery will be approached by their anesthesia providers.
Those who will be accepted to participate in the study were screened for inclusion and
exclusion criteria on the day of the surgery or one day before. Informed consent will be
taken from all participants by anesthesia providers. The duration of the study will be from
the start of cardiac surgical procedure till after separation from CPB by 60 minutes.
Patients will be included in the study are aged from18- 60 yrs old undergoing CABG and/or
valve surgery on CPB and have 2 or more preoperative risk factors for Vasoplegia including
- Using preoperative beta blocker (BB) or Angiotensin converting enzyme inhibitor (ACEI).
- preoperative EF < 35%
- History of thyroid disease
- Preoperative diuretics
Exclusion criteria are:
1. Emergency surgery
2. Severe renal Insufficiency (preoperative Cr > 1.8 mg / dL)
3. Severe hepatic disease (preoperative diagnosis of liver cirrhosis or recent elevated
liver function tests
4. Pregnant or woman of child bearing potential
5. Know hypersensitivity to hydroxycobolamin
Preoperative data will be obtained from the medical records and verified with the patients;
sex, age, Body surface index (BSI) , height and weight, type of surgery , preoperative use of
;ACEI- BB- calcium channel blocker (CCB) - amiodarone, mean arterial blood pressure (MAP),
preoperative Ejection fraction (EF). Anesthesia will be induced in all patients and
maintained by using midazolam, fentanyl, propofol, sevoflurane, pancurium.
- All patients were monitored with the routine monitoring of all cardiac patients which
included: MAP in mmHg, oxygen saturation (SaO2), central venous pressure (CVP) in cmH2o,
electrocardiography (ECG), Cardiac output (CO) L/min, arterial blood gases (ABG)
measuring; PH, PaCo2, HCO3, lactate during the pre- during- post CPB, trans-esophageal
echocardiography (TEE) measuring CO, CI, LVEF, SVR ( dyne.s/cm5)=MAP-CVP/CO✖ 800, SVRI=
MAP-CVP/ CI ✖ 800.
Vasopressors in the form of norepinephrine will be started and titrated to maintain MAP >60
mmHg in the pre- during - post CPB period.
The total doses of norepinephrine and epinephrine (if needed) in (µg/kg/min) will be recorded
on the anesthesia record by anesthesia providers. After induction of CPB all patients undergo
non pulsatile hypothermia (32-34 0C) CPB with a membrane oxygenator and the arterial line
filter. Priming of CPB will be done by crystalloids and serial HCT level were at >18%. The
flow rate on CPB was 2- 2.5L/ min/ m2 to maintain the MAP 50-80 mmHg. Blood gases samples
will be measured every 30 min to maintain arterial CO2 of 35-40 mmHg uncorrected for
temperature (alpha stat) and the partial pressure of O2 (150-250 mmHg). Hemodynamics will be
recorded every 30 min intervals and stored into the anesthesia record. The time of CPB and
cross clamping time will be recorded.
At the end of CPB, the patients will be assigned randomly into 2 groups by using computer
generated random numbers sequences and sealed envelopes.
Group (OH CO): 30 patients will receive hydroxycobolamin (Cyanokit) 5 gm intravenously(iv)
through the central venous catheter as bolus over 15 min reconstituted in 200 ml of NS.
Group (C) control: 30 patients will receive 200ml of NS over 15 min iv.
Primary outcome will be change in MAP between baseline and all time points (30 & 60 min after
CPB initiation) and (30 & 60 min after CPB separation) between the two groups and within the
same group.
Secondary outcomes were:
1. Change in SVR between baseline and all time points (30 & 60 min after CPB initiation)
and (30 & 60 min after CPB separation) between the 2 groups and within the same group.
2. Number of patients who needed norepinephrine ≥ 0.5µg/kg/min ± epinephrine as inotropic
support during weaning from CPB.
3. Incidence of vasoplegic syndrome occurrence which is defined as occurrence of one or
more of these parameters: systemic vascular resistance of ≤ 800 dyne/ s/ cm, an MAP of ≤
60 to 65 mm Hg, a cardiac index of ≥ 2.5 to 3 L/ min/ m2, a requirement for at least one
or more high-dose of vasopressors (ie, norepinephrine >0.05 μg / kg/ min).
4. Number of patients who developed norepinephrine refractory vasoplegia ( needed
epinephrine as another inotropic support)
5. Number of patients developed multiorgan failure in ICU
6. Mortality rate.
