Patient-Controlled Sedation in Port Implantation (PACSPI-2)

Study Overview
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Brief Summary
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The goal of the study is to determine if patient-controlled sedation (PCS) with propofol and alfentanil reduces patient-reported pain perception during implantation of subcutaneous venous port (SVP). The main question it aims to answer: How much pain did you (patient) experience during SVP-implantation Several other questions will be answered regarding: patient´s perception of the procedure, complication rate, procedure data. The study contains two groups which will be compared. Control group: will do SVP implantation under local anaesthesia Study group: will do SVP implantation under local anaesthesia and patient-controlled sedation. The patients are asked to complete a questionnaire postoperatively which contains questions on pain perception and satisfaction.

Detailed Description
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The study is an open multicentre randomized controlled trial with a study and a control arm in a 1:1 ratio. Patients will be randomized to either a control arm of LA for SVP-implantation or a study arm of PCS with propofol and alfentanil as adjunct to LA for SVP-implantation. The aim is to randomize 340 patients with an estimated patient recruitment over 18 months with a following 6 months of data cleaning and analysis. The trial will be performed at two centres; County Hospital Ryhov, Jönköping, Sweden and University Hospital Linköping, Sweden. SVP implantation procedure and perioperative time period is estimated to 2-4 hours. The primary endpoint is assessment of patients´ self-reported pain perception. Secondary outcomes include patient satisfaction, implantation conditions, sedation level, sedative and analgesic medication consumption, procedural time consumption as well as safety aspects, adverse events and estimation of perioperative experience. Participation in the trial ends after telephone inquiry one day postoperatively. Control arm: SVP-implantation in LA: Subcutanous venous ports were introduced in 1981. A SVP is a small device around 3cm in diameter with an injectable membrane buried just under the skin. It is connected to a thin tube with its tip in a large bore vein. Access to the SVP is achieved by puncturing the skin with a needle. Local anaesthetic causes the absence of pain sensation in the location where applied by decreasing the rate of depolarization and repolarization of excitable membranes such as nociceptors and nerves. The most commonly used solutions are from the amide group differing in pharmacokinetics. In order to reduce a burning sensation on infiltration substances can be combined with sodium bicarbonate. There will be no restrictions in the choice of LA-solution being left up to local practice at participating sites. With the beginning of the procedure LA is subcutaneously applied to patients in both groups. LA used at participating centres are Mepivacaine 10mg/ml, 20-40ml subcutaneously or Lidnocaine 10mg/ml, 20-40 ml subcutaneously. Study arm: SVP-implantation in LA and PCS: In addition to LA, patients in the study group are able to self-administer a combination of propofol and alfentanil using a patient-controlled sedation pump. The pump enables the patient via a hand-held button to trigger the release of a single bolus of 0.5ml containing 4.5mg propofol and 25µg alfentanil under an 10 second period. This results in a maximal possible amount of 6 bolus doses per minute. Propofol is a short-acting anaesthetic agent commonly used for general anaesthesia and procedural sedation. Several mechanisms of action have been proposed both through potentiation of GABAA receptor activity and in higher doses behaving as GABAA receptor agonist. When used for intravenous sedation a single dose wears off within minutes demanding for continuous or intermittent application. Alfentanil is a short-acting synthetic opioid analgesic agent with rapid onset of effects at µ-opioid receptors. These properties make it suitable to provide analgesia for brief procedures and to infuse for longer procedures and yet provide relatively rapid recovery. Rescue sedation will be available to patients in both groups on the patient´s or operator´s demand. Rescue sedation consists of propofol and alfentanil administered by the clinician and is documented in the e-CRF. Setting: This trial will be carried out in the following anaesthesia departments: OP/IVA clinic, County Hospital Ryhov, Sweden AnOpIVA clinic, University Hospital Linköping, Sweden Participants will be instructed on use of the PCS pump (Syramed µSP6000, Arcomed AG, Switzerland) by a nurse anesthetist. The syringe is loaded with 36 ml propofol (10 mg/ml) and 4 ml alfentanil (0.5 mg/ml). Each time the patient presses the handheld button, an aliquot of 0.5 ml is injected (4.5 mg propofol/0.025 mg alfentanil). The injection time is set to 10 s, restricting self-administration to a maximum of 6 bolus doses per minute corresponding to 27 mg propofol and 0.15 mg alfentanil per minute. No lockout period is applied. Local anaesthesia is injected in the operating site. Vital parameters prior to the procedure are recorded. Patients are monitored using electrocardiography for heartrate (HR), non-invasive blood pressure (BP), oxygen saturation (SpO2), and respiratory rate (RR) at 5-min intervals during the procedure. Bradycardia is defined as HR <40 beats/min, tachycardia as HR >100 beats/min, hypotension as systolic BP < 90 mmHg or a decrease of >30% from baseline, hypoxia as SpO2 <90% or a decrease of >5% from baseline, and bradypnea as RR of <8 breaths per minute. Supplemental oxygen via a capnograph-fitted nasal cannula is administered to all patients at 2 L/min during the procedure. The Observer's Assessment of Alertness/Sedation score (OAA/S) [9] is used to determine the sedation level during the four procedural steps: 1) sterile swabbing, 2) injection of LA, 3) catheter tunneling, and 4) sterile drape removal. The operating anesthesiologist assesses the operating conditions on a 4 point scale with 1 enabling the operator to perform the procedure without time delay and 4 having to abort the procedure. Puncture attempt is defined as continuous needle advancement to establish vein puncture. An unvalidated patient perception assessment tool with seven dimensions applying the NRS is used to evaluate patient perception. QoR-15 will be measured att 3 timepoints. Preoperatively, postoperatively before patient discharge and one day postoperatively.

Official Title
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Patient-Controlled Sedation in Port Implantation (PACSPI-2) -a Randomized Controlled Trial

Conditions
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Pain, Patient Satisfaction, Cancer, Venous Puncture

Intervention / Treatment
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* Drug: Propofol + Alfentanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥18 years with cancer in need of SVP. Exclusion Criteria: Inability to operate the PCS apparatus. Inability to communicate in Scandinavian languages. Patients who require general anaesthesia or patients eligible for LA only on anesthesiologist´s assessment (i.e. severe sleep apnea). Propofol or alfentanil allergy. Non-fasting according to guidelines of the Swedish Society for Anaesthesia and Intensive Care (SFAI). Failure to achieve peripheral vascular access. Pregnancy Previous participation in study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 110 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control arm (LA)<br>Patients in this arm will undergo SVP insertion in local anesthesia (LA) | |
| Active Comparator: Study arm (LA+PCS)<br>Patients in this arm will undergo SVP insertion in local anesthesia and PCS (LA+PCS) | Drug: Propofol + Alfentanil<br>* In addition to LA, patients in the study group are able to self-administer a combination of propofol and alfentanil using a patient-controlled sedation pump. The pump enables the patient via a hand-held button to trigger the release of a single bolus of 0.5ml containing 4.5mg propofol and 25µg alfentanil under an 10second period. This results in a maximal possible amount of 6 bolus doses per minute.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal intraprocedural pain level on numeric rating scale | NRS Participants assessment of maximal pain level experienced during the procedure using a numeric rating scale from 0-10 (0=no pain, 10=worst pain I know) on patient questionnaire. | after completion of procedure 10 minutes before discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants overall satisfaction, Participants satisfaction with staff | NRS Participants assessment of overall satisfaction experienced during the procedure using a numeric rating scale from 0-10 (0=not satisfied at all, 10=very satisfied) on patient questionnaire | after completion of procedure 10 minutes before discharge | 
| Number of participants with arterial puncture, pneumothorax, bradycardia, hypoxia, airway intervention, bradypnea | Respiratory and circulatory complications as well as mechanical complications during the procedure bradycardia: defined as heart < 40/minutes during the procedure Hypoxia: defined as Oxygen saturation <90% or significant drop from baseline (>5% SaO2 drop) during the procedure Airway intervention: defined as intervention by staff with chin lift during the procedure bradypnea: defined as respiratory rate <8/minute during the procedure | during the procedure | 
| Sedation score on Observers Assessment of Alertness/Sedation scale (OAA/S) | Sedation levels according to Observers Assessment of Alertness/Sedation scale 5: responds readily to naame spoken in normal tone 4: responds lethargically to name spoken in normal tone 3: responds only after name is called loudly, repeatedly, or both 2: responds only after mild prodding or shaking 1: responds only after painful trapezius squeeze 0: does not respond to painful trapezius squeeze | during procedure at time point T1: sterile skin prepping; T2: local anaesthetic injection; T3: tunneling procedure; T4: draping removal | 
| type of catheter | Procedural measures | during the procedure | 
| amount and type of local anaesthesia | Procedural measures | during the procedure | 
| amount of sedative medication given | Procedural measures | during the procedure | 
| time consumption of the procedure | Procedural measures | during the procedure | 
| number of puncture attempts | Procedural measures | during the procedure | 
| use of ultrasound | Procedural measures | during the procedure | 
| positioning of catheter tip | Procedural measures | during the procedure | 
| vessel choice | Procedural measures | during the procedure | 
| Quality of Recovery QoR-15 questionnaire | Quality of Recovery according to QoR-15 Have you had any of the following in the last 24 hours? 10 to 0, where: 10 = none of the time [excellent] and 0 = all of the time [poor]) Able to breathe easily Been able to enjoy food Feeling rested Have had a good sleep Able to look after personal Able to communicate with family or friends Getting support from hospital doctors and nurses Able to return to work or usual home activities Feeling comfortable and in control Having a feeling of general well-being Moderate pain Severe pain Nausea or vomiting Feeling worried or anxious Feeling sad or depressed | by telephone the day after the procedure | 
| Quality of Recovery QoR-15 questionnaire | Quality of Recovery according to QoR-15 | before the procedure at arrival to preoperative unit | 
| Quality of Recovery QoR-15 questionnaire | Quality of Recovery according to QoR-15 | within 1 hour after completion of procedure | 
| Participants evaluation of the importance of receiving sedatives during the procedure Participants evaluation of the importance of being in control of sedation administration | Participants assessment of the importance of receiving sedatives and being in control of sedation on a numeric rating scale from 0-10 (0=not important, 10=very important) on patient questionnaire | within 1 hour after completion of procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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patient-controlled sedation, totally implantable venous access device, subcutaneous implanted venous port, local anesthesia, propofol, alfentanil, indwelling catheter