Dexmedetomidine Versus Dexamethasone as Adjuncts in Erector Spinae Plane Block in Modified Radical Mastectomy
Condition: Breast Cancer; Post Operative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional

Summary: 
      The aim of this study is to evaluate the analgesic efficacy and safety of adding
      dexmedetomidine versus dexamethasone to levobupivacaine in ultrasound guided ESPB for
      patients undergoing modified radical mastectomy
    

Detailed description: 
      Breast cancer is the most common malignancy among females. Modified Radical Mastectomy (MRM)
      is one of the main surgical treatments of breast cancer .The most common modality for
      anesthesia is general anesthesia with or without regional blocks . Nearly 40-60% of patients
      undergoing breast surgery experience severe acute postoperative pain, with severe pain
      persisting for 6-12 months in almost 10-30% of patients (Post Mastectomy Pain Syndrome; PMPS)
      . This pain can be severe enough to cause long-term disabilities and interfere with sleep and
      performance of daily activities.

      Postoperative pain is usually managed by opioids, yet it is usually associated with side
      effects including; prolonged sedation, increase in the incidence of recurrence, respiratory
      depression , nausea , vomiting and ileus. In an attempt to reduce these side effects,
      thoracic epidural analgesia and paravertebral block became the gold standard regional
      techniques for breast surgery. However, both techniques may be associated with serious
      complications such as pneumothorax, spinal cord injury, incompatibility with pre-existing
      anticoagulation or antiplatelet therapy and hemodynamic instability. Multiple different
      regional techniques have been developed in the last decade for postoperative pain management
      of MRM including including erector spinae plane block (ESPB) aiming to be effective and
      associated with less complications when compared to the gold standard techniques .

      ESPB is a simple and safe paraspinal fascial plane block that involves injection of local
      anesthetic deep in the erector spinae muscle and superficial to the tips of the thoracic
      transverse processes hoping to block both ventral and dorsal rami of spinal nerves in the
      paravertebral area. However, regional blocks after a single dose of local anesthetic are of
      limited duration and efficacy. Hence, the co-administration of adjuvants with local
      anesthetics may be helpful for prolongation and potentiation of the analgesic effect.
      Dexmedetomidine is a potent α2agonist of which α2/α1 selectivity is 8 times greater than
      clonidine and is now emerging as an adjunct to regional and general anesthesia. It can
      prolong the duration of the nerve block when used with a local anesthetic .Dexamethasone is
      considered as an adjuvant as it act by reducing the release of inflammatory mediators and by
      inhibiting discharge of C-fibers. There is a limited number of studies covering the effect of
      dexmedetomidine versus dexamethasone when added to ESPB, yet they are still lacking in breast
      surgeries. Our study aims at studying the effect of adding dexmedetomidine compared to
      dexamethasone as adjuncts to ESPB in modified radical mastectomy.

      Objectives:

      To identify the intraoperative and postoperative opioid consumption, as well as duration of
      analgesia and study the effect on hemodynamics.

      Hypothesis We hypothesize that the addition of dexmedetomidine to levobupivacaine in US
      guided ESPB in patients undergoing MRM is superior to either adding dexamethasone to
      levobupivacaine, or using levobupivacaine alone.

      Ethical Considerations The trial will be conducted after approval of departmental and
      institutional research ethics committee. A written informed consent will be obtained from all
      participants.

      A comparative double-blinded study.

      Study setting and location The study will be conducted in the breast operating theatre at
      National Cancer Institute hospital.

      Study population 90 Female patients ASA II,III scheduled for modified radical mastectomy
      under general anaesthesia.

      A. preoperative:

      Patient's assessment; History, physical exam, laboratory and radiological investigations at
      preoperative assessment clinic National Cancer Institute Cairo University. Preoperative
      assessment on the night of surgery. Patients will be instructed on how to report pain by
      means of Numeric Pain Rating Scale, in which 0 = "no pain" and 10 = "worst possible pain". An
      informed consent will be obtained. Preoperative fasting; minimum of 6 hours for food and
      minimum of 2 hours for water and clear fluids.20G IV cannula is inserted. All patients will
      be pre-medicated with IV midazolam 0.01-0.02 mg\kg 30 minutes preoperatively. ESPB with
      either adjuncts or none at all will be done preoperatively with the patients in a lateral
      position. After allocation of patients to each study group, patients in group 1 will receive
      dexmedetomidine with levobupivacaine in ESPB, while patients in group 2 will receive
      dexamethasone with levobupivacaine in ESPB, & patients in group 3 will receive
      levobupivacaine without adjuncts in ESPB.

      Technique of ESPB: The block level will be at T5 with the patient in a lateral position. The
      ultrasound probe will be placed on the back in a transverse orientation to identify the tip
      of the T5 transverse process; these are recognizable as flat, squared-off acoustic shadows
      with only a very faint image of the pleura visible. If the transducer is too lateral, the
      ribs will be visualized instead; these are recognizable as rounded acoustic shadows with an
      intervening hyperechoic pleural line. The tip of the transverse process will be centered on
      the ultrasound screen and the probe will then be rotated into a longitudinal orientation to
      produce a parasagittal view, in which the following layers will be visible superficial to the
      acoustic shadows of the transverse processes: skin, subcutaneous tissue, trapezius, erector
      spinae muscle and T5 transverse process. A skin wheel using 3 ml of lidocaine 1% is made 2-3
      cm above the upper aspect of the transducer, then an echogenic block needle will be inserted
      in plane to the ultrasound beam in a cranial-to-caudal direction until contact is made with
      the T5 transverse process. Correct location of the needle tip in the fascial plane deep to
      erector spinae muscle will be confirmed by injecting 0.5-1 ml glucose 5% and seeing the fluid
      lifting the erector spinae muscle off the transverse process without distending the muscle.
      After aspiration; to avoid intravascular injection, 30 ml levobupivacaine 0.25% to which
      dexmedetomidine (1microgram\kg) is added in the first group , while dexamethasone (10 mg) is
      added to levobupivacaine in the second group, and no adjuncts to levobupivacaine is added to
      the third group. Upon injection, separation will be seen. 6-13-MHz, linear transducer set for
      small parts and a depth of 4-6 cm will be used. Fujifilm Sonosite M-Turbo Ultrasound system
      will be used.

      B. Intraoperative:

      All patients will be monitored continuously using electrocardiography, non-invasive blood
      pressure, peripheral oxygen saturation and end tidal carbon dioxide throughout the duration
      of the surgical procedure. Induction of general anesthesia will be performed using a regimen
      of IV 2 μg/kg fentanyl and propofol IV 2 mg /kg. Tracheal intubation will be facilitated by
      using 0.5 mg/kg IV of atracurium. Anesthesia will be maintained with inhaled sevoflurane
      2-2.5% in oxygen enriched air (FiO2=0.5). Maintenance doses of atracurium o.1 mg\kg will be
      provided every 30 minutes. Paracetamol 500 mg and IV ketorolac 30mg will be provided as a
      part of multimodal analgesia. Rescue analgesia of fentanyl 1 μg/kg will be given if the mean
      arterial blood pressure or heart rate rises above 20% of the baseline levels. Ringer acetate
      will be infused to replace the fluid deficit, maintenance and losses, and patients will be
      mechanically ventilated at an appropriate setting keeping the end-tidal CO2 at 30- 35 mmHg.
      The first reading of mean arterial pressure (MAP) and heart rate (HR) will be taken before
      induction of general anesthesia to be defined as a baseline reading, another reading will be
      taken immediately before surgical incision and at 30-minute intervals intraoperatively. The
      residual neuromuscular blockade will be reversed using neostigmine (0.05 mg/kg) and atropine
      (0.02 mg/kg). Extubation will be performed after complete recovery of the airway reflexes.

      C. postoperative:

      Patients will be transferred to the post-anesthesia care unit (PACU) where the Numeric Pain
      Rating Scale score, MAP and heart rate will be noted immediately on arrival, then observed
      for 2 hours & discharged to the ward afterwards. Rescue analgesia will be provided in the
      form of IV morphine 3 mg boluses if the patient indicates Numeric Pain Rating Scale ≥ 4. The
      total amount of morphine given in 24 hours will be recorded for the three groups. A maximum
      dose of 0.5 mg/kg/24hours of morphine is allowed. IV paracetamol 500 mg \6 hours and IV
      ketorolac 30mg\8 hours will be given as a part of multimodal analgesia. Numeric Pain Rating
      Scale score, MAP and heart rate will be noted at 4, 8, 12, 16, 20 and 24 hours
      postoperatively. Side effects such as nausea, vomiting, sedation, respiratory depression
      (respiratory rate <10/minute) will be recorded. Postoperative nausea and vomiting (PONV),
      will be rated on a four-point verbal scale; (none =no nausea, mild =nausea but no vomiting,
      moderate=vomiting one attack, severe =vomiting >one attack). 0.1 mg/kg of IV ondansetron will
      be given to patients with moderate or severe postoperative nausea and vomiting . Sedation
      will be assessed in the PACU with Ramsay scores.(1 = anxious or restless or both; 2 =
      cooperative, orientated, and tranquil; 3= responding to commands; 4 = brisk response to
      stimulus; 5 = sluggish response to stimulus; and 6 = no response to stimulus). A Ramsay score
      of 5 or 6 will be considered excessively high sedation levels; a Ramsay score of 2 to 4 will
      be considered adequate sedation levels needing observation; a Ramsay score of 1 will be
      considered inadequate or insufficient sedation levels .

      Sample size As there was no study reporting results on a similar hypothesis, sample size was
      calculated based on the results of pilot study;SPSS version 23.0 was used to generate a list
      of 20 subjects who were randomly assigned into two groups each of 10 for the following
      treatment A) ESPB + Dexamethasone B) ESPB + Precedex Assuming a pooled standard deviation of
      2.37 units, the study would require a sample size of thirty for each group (i.e. a total
      sample size of 60, assuming equal group sizes), to achieve a power of 90% and a level of
      significance of 1% (two sided), for detecting a true difference in means of post operative
      morphia consumption between ESPB + Dexamethasone and ESPB + Precedex groups of -2.4 (i.e. 2.4
      - 4.8) units.

      Statistical analysis PSS version 27.0 will be used in data analysis. Quantitative variables
      were tested for normality to select appropriate statistical tests. Mean and standard
      deviation described quantitative data with median and range. Comparison of means (or medians)
      of two independent groups will be done using t test. To show the effect of time on vitals,
      parametric repeated measures ANOVA or Friedman test will be used to show changes overtime
      both intra and post-operative. Post-hoc test will be used for pairwise comparisons and will
      be Tucky adjusted. Chi-square and Fisher Exact were used for testing proportion independence.
      P value was always two tailed and set significant at 0.05 level
    

Intervention name(s): Adjuncts to levobupivacaine in Erector Spinae Plane Block
Intervention type(s): Procedure
Intervention description(s): The block level will be at T5 with the patient in a sitting position and full aseptic precautions. T5 transverse process; these are recognizable as flat, squared-off acoustic shadows with only a very faint image of the pleura visible. In a longitudinal US view, in which the following layers will be visible superficial to the transverse processes: skin, subcutaneous tissue, trapezius, erector spinae muscle . Skin is topicalized, then echogenic block needle inserted in plane to the ultrasound beam in a cranial-to-caudal direction until contact is made with the T5 transverse process. After aspiration; to avoid intravascular injection, 30 ml of injectate is injected and separation will be seen. 6-13-MHz, linear transducer set for small parts and a depth of 4-6 cm will be used (18-19).
Intervention MeSH terms: Levobupivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Modified Radical Mastectomy; Dexmedetomidine; Dexamethasone; Erector Spinae Plane Block; Regional anesthesia