Effects Of Patient-controlled Intravenous Analgesia With And Without A Low Basal Infusion On Postoperative Hypoxemia After Gastrointestinal Tumor Surgery

【Background】Postoperative pain is one of perioperative management’s most essential and complex points.Patient-controlled intravenous analgesia（PCIA）is widely used in postoperative analgesia in patients with gastrointestinal tumors because of its stable analgesic concentration,effective pain relief,simple administration,and substantial patient autonomy.The common analgesics of PCIA are opioids,which inevitably bring side effects such as nausea,vomiting,and respiratory depression.When patients receive PCIA,the guideline prioritizes no basal infusion because some studies have shown that extra basal infusion to PCIA does not improve pain scores and increases the risk of opioid-induced respiratory depression（OIRD）.However,most of these results were from morphine PCIA at high basal infusion,which may not apply to other opioids or low background doses.Hydromorphone is a semi-synthetic opioid with about 5-10 times more analgesic potent and fewer side effects than morphine.In recent years,several studies on PCIA with hydromorphone have found that a low basal infusion can better improve postoperative pain in patients undergoing thoracic and abdominal surgery than PCIA with a no-basal infusion.However,whether low-basal infusion increases the risk of OIRD relative to no basal infusion has not been investigated.Continuous monitoring of vital signs with wireless wearable devices can more accurately identify postoperative hypoxemia.Based on this,we designed a single-center,randomized,parallel-controlled,double-blind,non-inferior clinical trial to investigate whether a low-basal infusion of hydromorphone PCIA was non-inferior to a no-basal infusion in terms of postoperative hypoxemia after gastrointestinal tumor surgery.【Aims】The primary aim of this study was to investigate the occurrence of hypoxemia during the first 48 postoperative hours in patients receiving PCIA with and without low basal infusion.The secondary aims were to compare the effects of low-basal and no-basal infusions on hydromorphone consumption,analgesia,adverse events,and ambulation.【Methods】The clinical trial was conducted at the First Affiliated Hospital of Air Force Military Medical University.160 patients undergoing gastrointestinal tumor surgery were enrolled and randomly given either a low-basal or no-basal infusion of hydromorphone PCIA at 1:1after the operation.The analgesic drugs in both groups were hydromorphone 0.1mg/ml.Low-basal group:basal infusion of 1 ml/h,demand dose of 1 ml,lockout interval of 10minutes.No-basal group:basal infusion of 0 ml/h,demand dose of 2 ml,lockout interval of10 minutes.All the researchers,except the anesthetic nurse responsible for the analgesic pump preparation,were blinded to group allocation.All patients received postoperative PCIA and48-hour continuous vital signs monitoring with wireless e PM/ep pod to collect data such as pulse oxygen saturation（Sp O₂）and ambulation duration.Designated researchers conducted regular follow-ups.The primary outcome was the area under the curve（AUC）for hypoxemia（defined as Sp O₂<95%）per hour.The secondary outcomes were the AUCs for hypoxemia defined as Sp O₂<90%and<85%per hour,hydromorphone consumption,the Overall Benefit of Analgesia Score（OBAS）at postoperative 24 and 48 hours,Numeric rating scale（NRS）pain score at postoperative 4,24 and 48 hours,and the ambulation time per hour over 48 hours.Mann-Whitney U test was used to compare the AUCs for hypoxemia and hydromorphone consumption;the ambulation time was compared using Student’s t-test;the generalized linear mixed model（GLMM）was used to compare NRS pain score and OBAS score between groups.Subgroup analysis was conducted based on five baseline variables.The primary analysis was based on Intention-to-treat（ITT）,and Per-protocol（PP）sets as a sensitivity analysis.【Results】1)Of the 160 randomized patients,159 completed the trial;the baseline variables were similar between the low-basal and no-basal groups.2)In terms of the primary outcome,the hourly AUC（Sp O₂<95%）of hypoxemia in the low-basal group was significantly higher than that in the no-basal group,with a median difference of 0.097（95%CI:0.001-0.245）,and the estimated ratio of means was 2.146（95%CI:2.138-2.155）,which was worse than the non-inferiority margin of 1.25.3)Regarding the secondary outcomes,the hydromorphone consumption of low-basal infusion PCIA was significantly higher than that of the no-basal infusion.There was no significant difference between the two groups in the AUC for hypoxemia at two other definitions,NRS pain score,OBAS score,and ambulation time.4)The results of sensitivity analysis are consistent.5)There was no interaction between all subgroup variables and the intervention effect.【Conclusions】Among patients receiving hydromorphone PCIA after gastrointestinal tumor resection,the low-basal infusion was inferior to no-basal infusion PCIA for postoperative hypoxemia at Sp O₂<95%for the first 48 h after surgery.No-basal infusion mode should be preferred when such patients were treated with PCIA selected for multimode analgesia.