This will be a triple-blinded, individually-randomized, single-centered, placebo-controlled
trial in which patients will be randomly allocated to two study groups in a 1:1 ratio.
Randomization: The investigators will randomize patients in blocks of 4 or 6. The
randomization sequence will be generated online using Sealed Envelope (sealedenvelope.com) .
Allocation to treatment versus control will be placed in sealed envelopes. The envelopes will
be sequentially numbered, signed and opaque, with the randomization group insert wrapped in
foil, and further blocked by carbon paper. On the day of surgery, the regional
anesthesiologist be provided the envelope by the research assistant. They will to open it in
private, and then destroy its contents immediately upon reading the allocation card.
This study observes blinding of the patients, anesthesiologists, surgeons, nurses, outcome
collectors, and data analysts. Only the regional anesthesiologist performing the intervention
will be unblinded. To preserve blinding for everyone else, only the regional anesthesiologist
and anesthesia assistant will be present in the room at the time of block. Windows on the
operating room doors will be covered and a sign mounted to limit entry unless there is an
emergency.
Eligible patients will be identified in the Pre-assessment Clinic (PAC) or the inpatient
ward. Potentially eligible participants will be screened for significant cognitive
impairment, and those scoring 1-2 on the Mini-Cog will be excluded. Enrolled patients will
complete a baseline QoR-15 survey. Patients will then be provided a study information package
which they can then review on their own time. On the day of surgery, the unblinded regional
anesthesiologist will receive information on patient allocation from sealedenvelopes.com and
perform the study procedure in the operating room with arterial line monitoring prior to
induction of anesthesia. anesthesiologist.
Patients will remain intubated following surgery and be transferred to the CSICU where they
are usually extubated within 4-6 hours. Following extubation, patients will receive pain
management using hydromorphone IV until transfer to the ward or for the first 24 hours
(whichever comes first). For the remainder of the study, the patient will be prescribed a
standard postoperative pain control regimen and management will be at the discretion of
attending CSICU intensivist, cardiac surgeon or nurse practitioner without influence from
this study.
All patients will be followed from the time of randomization thereafter until the common
study end date (to be determined, approximately 2 years after the first patient randomized).
Primary analysis will be intent to treat.
Statistical Analysis
Sample size: A sample size of n = 112 per group, or total of N=224 patients will be required
to reject a null hypothesis that there is no difference in QoR-15 at 24 hours (Student's t
test), at a 2-sided alpha of 0.05, and a power of 80% (UBC Sample Size Calculator). This is
based off a Minimally Clinically Important Difference of 8.0 in a mixed population of
surgical patients reported by Myles et al. At St. Paul's Hospital, the investigators
conducted a preliminary prospective study assessing QoR-15 scores in 70 patients
approximately 24 hours following cardiac surgery found a lower mean (SD) QoR-15 score of
83.47 +/- 19.86 (unpublished data) than what has been published in the original validation
study of QoR-15. The investigators used the QoR-15 scores at 24 hours and a MCID of 8 to
calculate a sample size of n=97 per arm. The sample size will be increased by 15% to account
for a dropout rate of 5% and delirium rate of 10% observed at St Paul's Hospital, to arrive
at a sample size of n=112 per group, or total of N=224 for the entire study.
Primary analysis: intention-to-treat comparison on QoR-15 score at 24 hours (PVB vs sham
block) using Student's t test or Mann-Whitney U test). There will be a secondary efficacy
analysis done for per protocol population, which would exclude major protocol deviations. In
addition, the investigators will conduct a multiple linear regression analysis between the
primary outcome of QoR-15 score at 24 hours and treatment group adjusted for baseline QoR-15
score and baseline characteristics (age, sex, history of chronic pain prior to surgery,
history depression requiring medication, history of anxiety requiring medication, history of
poorly-controlled post-surgical pain, surgical risk stratification (Euroscore II). The
primary analyses will be conducted at a two-sided significance level of 0.05
Secondary Analysis: Continuous variables including cumulative opioid consumption, simplified
PONVIS score, VISmax score, duration of mechanical ventilation and length of stay will be
Eligible patients will be identified in the Pre-assessment Clinic (PAC) or the inpatient
ward. Potentially eligible participants will be screened for significant cognitive
impairment, and those scoring 1-2 on the Mini-Cog will be excluded. Enrolled patients will
complete a baseline QoR-15 survey. Patients will then be provided a study information package
which they can then review on their own time. On the day of surgery, the unblinded regional
anesthesiologist will receive information on patient allocation from sealedenvelopes.com and
perform the study procedure in the operating room with arterial line monitoring prior to
induction of anesthesia. anesthesiologist.

Patients will remain intubated following surgery and be transferred to the CSICU where they
are usually extubated within 4-6 hours. Following extubation, patients will receive pain
management using hydromorphone IV until transfer to the ward or for the first 24 hours
(whichever comes first). For the remainder of the study, the patient will be prescribed a
standard postoperative pain control regimen and management will be at the discretion of
attending CSICU intensivist, cardiac surgeon or nurse practitioner without influence from
this study.

All patients will be followed from the time of randomization thereafter until the common
study end date (to be determined, approximately 2 years after the first patient randomized).
Primary analysis will be intent to treat.

Statistical Analysis

Sample size: A sample size of n = 112 per group, or total of N=224 patients will be required
to reject a null hypothesis that there is no difference in QoR-15 at 24 hours (Student's t
test), at a 2-sided alpha of 0.05, and a power of 80% (UBC Sample Size Calculator). This is
based off a Minimally Clinically Important Difference of 8.0 in a mixed population of
surgical patients reported by Myles et al. At St. Paul's Hospital, the investigators
conducted a preliminary prospective study assessing QoR-15 scores in 70 patients
approximately 24 hours following cardiac surgery found a lower mean (SD) QoR-15 score of
83.47 +/- 19.86 (unpublished data) than what has been published in the original validation
study of QoR-15. The investigators used the QoR-15 scores at 24 hours and a MCID of 8 to
calculate a sample size of n=97 per arm. The sample size will be increased by 15% to account
for a dropout rate of 5% and delirium rate of 10% observed at St Paul's Hospital, to arrive
at a sample size of n=112 per group, or total of N=224 for the entire study.

Primary analysis: intention-to-treat comparison on QoR-15 score at 24 hours (PVB vs sham
block) using Student's t test or Mann-Whitney U test). There will be a secondary efficacy
analysis done for per protocol population, which would exclude major protocol deviations. In
addition, the investigators will conduct a multiple linear regression analysis between the
primary outcome of QoR-15 score at 24 hours and treatment group adjusted for baseline QoR-15
score and baseline characteristics (age, sex, history of chronic pain prior to surgery,
history depression requiring medication, history of anxiety requiring medication, history of
poorly-controlled post-surgical pain, surgical risk stratification (Euroscore II). The
primary analyses will be conducted at a two-sided significance level of 0.05

Secondary Analysis: Continuous variables including cumulative opioid consumption, simplified
PONVIS score, VISmax score, duration of mechanical ventilation and length of stay will be
compared using Student's t test or Mann-Whitney U test, or repeated measures ANOVA with
Bonferoni correction when applicable. Dichotomous variables such as atrial fibrillation,
pulmonary complications, delirium, and adverse events will be compared using Chi-Squared test
or Fisher's Exact Test, or repeated measures ANOVA with Bonferroni correction when
applicable. Area under the pain intensity curve (AUE) derived from NRS-11 pain scores
obtained from the 4th to 48th hour, and QoR-15 scores at baseline, 24 hours, 48 hours and 12
weeks will be analyzed using a mixed models for repeated measures (MMRM), with baseline
values, study group, study visit, and the interaction between study visit and study group as
covariates. The analysis of secondary outcomes will be conducted at a two-sided significance
level of 0.05.
Handling of Missing data: There will be a proportion of patients who will have missing
outcomes due to complications such as delirium/confusion, delayed extubation, postoperative
bleeding, and hemodynamic instability. It is anticipated that the loss to follow-up to be
<15% which is considered in the sample size calculation. All efforts will be made to collect
complete data for all patients in this study. Patients will be followed till the study end
and will complete all required data collection. In general, missing values observed in the
study will be treated as 'missing'. No attempt will be made to impute missing values and only
observed values will be used for analysis.
Subgroup and Sensitivity Analysis: The investigators plan to conduct 3 subgroup analyses
based on sex, age, and patients with moderate to severe asthma or COPD. Sensitivity analysis
will be conducted comparing intent to treat versus per protocol analysis.