…intraoperative and postoperative analgesia for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A case report. (unpublished paper).
Intratechal Opioids Combined to Transversus Abdominis Plane Block Contribute to Effective Intraoperative and Postoperative Analgesia For Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Case Report.
Luciano A Gomez
Luciano A Gomez, Department of Anaesthesia, Institute of Oncology "Angel H. Roffo", University of Buenos Aires, Buenos Aires 1417, Argentina.
ORCID number: Luciano A Gomez (0000-0003-1683-538X)
Supportive foundations. The present work was not supported by any grant or other financial support.Authors Contributions: Luciano Ariel Gomez provided intraoperative patient care and wrote the manuscript.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and accompanying images.
Conflict-of-interest-statement: The author declare that he has no conflict of interest.
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Manuscript source: Submitted manuscript
Correspondence to: Dr Luciano Ariel Gomez. Instituto Oncológico Angel Roffo, Departamento de Anestesiología, Sector Cirugía, Pabellón Modelo, Av. San Martín 5481 (C1417DTB), Ciudad de Buenos Aires, Argentina.
E-mail: drlucianogomez@gmail.com
Phone: +5491169614371
Abstract
BACKGROUND
Cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) represents a challenge due to chemotoxicity and difficult management of pain, temperature and hemodynamic. Although thoracic epidural analgesia is the standard analgesic plan, it has been questioned due to the risk of hypotension, hematoma, infection and catheter problems. We report the combination of single shot intratechal morphine-fentanyl injection with bilateral oblique subcostal transversus abdominis plane block as an alternative strategy to provide perioperative analgesia, avoiding epidural induced sympathetic blockade in CRS-HIPEC.
CASE SUMMARY
A 64-year-old man (90kg, 181cm) with diagnosis of pseudomyxoma peritonei tumour presented to our hospital complaining of long lasting abdominal pain and increased abdominal size. Perioperative analgesic treatment included preoperative subarachnoid injection of morphine 650µg+ fentanyl 29.3µg and, after induction, bilateral oblique TAP block with bupivacaine 1.5mg/kg. Sevoflurane was adjusted to keep Bispectral IndexTM within a target range of 40 to 60. This resulted in a mean sevoflurane Minimum Alveolar Concentration of 0,645 (range 0,9-0,4). Intraoperatively the patient showed adequate anesthesia depth; there was no need of additional opioids.
Postoperative analgesia protocol included ruled lidocaine, diclofenac, acetaminophen, pregabalin and intravenous morphine if pain verbal analogue scale was>4. Morphine administration was only necessary on postoperative day 2 (3 doses, 2mg each); there was no need of additional opioid medication during the remaining hospital stay. The patient continued to be pain free and he was able to return to his habitual job.
CONCLUSION
Combining spinal opioids with wall blocks may provide analgesia for major abdominal surgery producing opioid sparing analgesia without sympathetic blockade.
Key words: Spinal analgesia; Pain; Perioperative; Intraoperative; HIPEC; Case report.
INTRODUCTION
Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC), a common treatment for peritoneal carcinomatosis, represents a complex challenge to the anesthesiologist due to chemotoxicity and difficult management of pain, temperature and hemodynamic[1,2]. CRS is usually an open surgery, requiring a xiphoid to pubis incision and extensive debulking that includes omentectomy, resection of peritoneal lesions, and often splenectomy, nephrectomy and/or segmentary gut resections. Intraabdominal extensive scarring and irritation by chemotherapy produce intense visceral pain, making CRS-HIPEC of the most painful surgery among all major abdominal surgeries[1,3]. Although thoracic epidural analgesia (TEA) is the standard procedure for CRS-HIPEC in experienced centers[2-4], it has been questioned due to the risk of hypotension, hematoma, infection and catheter problems[2,3,5-7] ; in addition, unsuccessful epidural placement in advance to CRS-HIPEC has been reported in 4 to 18% of the patients[3].
Preoperative intratechal opioid administration (PIOA) is a simpler technique, with minimal or absent hemodynamic effects[8], may provide intraoperative[9,10] and postoperative analgesia[9-13], and opioid[9,13] and volatile anesthestic[10,14] sparing effects. During PIOA morphine is usually administered, reaching a maximum abdominal analgesic effect in approximately two hours after lumbar injection[10], so it is necessary to provide analgesia until morphine has reached its peak effect. In the present case, we added a bilateral oblique subcostal transversus abdominis plane (TAP) block[15] and combined a short onset liposoluble opioid with intratechal morphine to improve analgesia during the initial phase of the surgery; so PIOA (morphine-fentanyl) + TAP block were combined to provide intra- and postoperative analgesia to this patient undergoing CRS-HIPEC. After searching in PubMed and Google engines using the keywords ‘Spinal analgesia,’ ‘Subarachnoid analgesia,’ ‘Intratechal morphine’, ‘Intratechal opioids´, ‘Spinal morphine’, ‘Subarachnoid morphine’ and ‘HIPEC’, ‘Hyperthermic chemotherapy’, ‘Heated chemotherapy’, we have not found previous reports, so to our knowledge this is the first description of opioid spinal analgesia in CRS-HIPEC procedure.
Written informed consent was obtained from the patient to publish this case report.
CASE PRESENTATION
Chief complaints
A 64-year-old man, with a medical history of arterial hypertension treated with enalapril 10mg daily, with a previous diagnosis of pseudomyxoma peritonei tumour was scheduled for CRS-HIPEC.
History of present illness
The patient complained of long lasting (more than five years) abdominal pain. His previous medical treatment included surgery (right hemicolectomy) and intravenous chemotherapy in other institution.
History of past illness
The patient began five years ago with abdominal pain located in the right abdomen, mainly in flank and hypochondrium. The pain had worsened two and half years ago and he underwent an exploratory laparotomy with hemicolectomy, and intestinal termino-terminal anastomosis. Surgical biopsy diagnosed low grade apendicular pseudomyxoma peritonei tumour. He then received XELOX intravenous chemotherapy scheme (oxaliplatin-capecitabine), without showing favourable results.
Physical examination upon admission
The patient (90kg, 181cm) showed a moderate increase of abdominal size. The abdominal wall was not tense and he did not present any respiratory, gastrointestinal or other major associated symptoms.
Laboratory examinations
Blood analysis revealed haematocrit 47%, haemoglobin 15,8g/dL and platelet count 181000/dL. Fibrinogen was 266mg/dL and the rest of blood chemistry, as well as the urine analysis, were normal.
Echocardiography report showed left ventricular ejection fraction of 60% (Simpson´s method), normal left ventricular diameter, mild septal hypertrophy, mild left ventricular diastolic dysfunction and mild mitral valve regurgitation.
Imaging examinations
SPECT/CT scan showed hipodense pseudonodular images surrounding the right portion of the liver and in the fat tissue of the mesenterium and major epiplon. An abnormal lesion measuring 26x33mm, with mild metabolic activity, was observed in the major epiplon. Moderate metabolic activity was found in the entire colon. The rest of abdomen and pelvis did not show abnormal tracer uptake areas.
Treatment
The patient received bowel preparation and clear liquids until 6 hours before surgery and, three hours before induction, an oral dose of pregabalin 150mg, acetaminophen 1g and maltodextrin 25g; antihypertensive medication was omitted.
PIOA was performed in the operating room, at the L2-L3 intervertebral space, with morphine 650µg+ fentanyl 29.3µg (total volume 0.65mL). Anesthesia was induced by face mask with sevoflurane and atracurium 0.6mg/kg intravenous (IV) was administered, followed with a 10µg.kg-1.min-1 infusion. After induction, the patient received IV ciprofloxacine 200mg, ornidazole 1g, omeprazole 40mg, dexamethasone 8mg and tranexamic acid 10mg/kg followed with a 1mg.kg-1.h-1 infusion.
Ultrasound-guided bilateral oblique TAP block was performed with bupivacaine 1.5mg/kg (total volume 90mL). Briefly, 25mL of anesthetic solution was injected, beginning in the subxiphoid area, where the transversus abdominis muscle becomes visible underneath the rectus abdominis muscle, and immediately lateral. A 20mL second injection of local anesthetic was placed in the TAP, lateral to the linea semilunaris, and midway between the inferior ribs and the iliac crest; the procedure was repeated at the contralateral side.
During anesthesia, sevoflurane dose was adjusted to keep Bispectral IndexTM (BIS) values within a target range of 40 to 60 (BISTM VISTA monitor application 3.2 platform 2.03, Aspect Medical System). Monitoring also included peripheral perfusion index (MindrayTM), nasopharyngeal and rectal temperature, continuous central venous pressure, arterial line and pulse pressure variation. Depth of neuromuscular block was quantitatively measured by acceleromyography (MindrayTM) and atracurium infusion was targeted to keep a train of four count <= 1 and a post-tetanic-count >=1. After peritoneal closure, atracurium infusion was discontinued and, at the end of surgery, IV neostigmine 0.06mg/kg, atropine 1mg and ondansetron 4mg were administered and tranexamic acid infusion was stopped.
Surgery began 60 minutes after PIOA, and 30 minutes after finishing the TAP block. Exploratory laparotomy showed peritoneal cancer index of 9 and absence of ascites; cytoreduction included resection of major and minor epiplon, gallbladder, prerenal and right diaphragmatic peritoneum, round ligament, and electrovaporization of hepatic implants. The physiological parameters measured before and after incision were: heart rate 51/54 beats/minute (+5,88%), medial arterial tension 59/66 mmHg (+11,86%), BIS 55/47 (-25,85%) and perfusion index 3,17/4 (+26,18%). CRS phase was followed by 90 minutes of HIPEC, using the open abdomen technique, also referred to as the “coliseum technique” (Figure 1), with mitomycin C 25mg/m2, diluted in 2,3% dextrose peritoneal dialysis solution (PeritosterilTM, Fresenius Medical Care), at a target temperature of 41-42°C.
During the surgical procedure, sevoflurane was administered at a mean Minimum Alveolar Concentration (MAC) of 0,645 (range 0,9-0,4) (age corrected MAC=1,764%) with higher sevoflurane requirements after induction and minimal during the first 60 minutes of HIPEC. Mean measured BIS was 58,83 (range 47-61); no burst suppression periods were observed. Intraoperatively, there was no need of additional opioids, vasoactive agents or hemoderivates.
During the CRS phase, hypothermia was prevented by forced air warming; during the HIPEC phase, active cooling with forced air, cold packs, and infusion of cold fluids (4°C) were used to prevent systemic hyperthermia.
The entire intervention took 647 minutes, and included the preparation for surgery (PIOA, anesthetic induction, bilateral TAP block) 92 minutes, the surgery 512 minutes, and 43 minutes to leave the operating room. The patient was extubated and transferred to the intensive care unit (ICU) breathing oxygen 50%.
Postoperative analgesia in the ICU included lidocaine 56mg/hour IV; diclofenac 75mg Q12 hours IV; acetaminophen 1g Q8 hours and pregabalin 75mg Q12 hours were administered via a nasogastric tube. Morphine 2mg IV was administered if verbal analogue score (VAS) was >4 (0=no pain, 10=worst imaginable pain). On postoperative day (POD) 1 the patient had good pain control and did not require morphine supplementation. On POD2, pregabalin was increased to 3 daily doses and lidocaine infusion suspended; this day the patient complained of pain VAS=5 and received 3 doses of morphine (total dose 6mg). The patient stayed in the ICU for 4 days, receiving diclofenac/paracetamol/pregabalin, as previously stated. He did not need additional opioid medication during the remaining hospital stay. Bladder catheter removal was in the morning of POD5 and the patient began with a solid diet on POD7.
Outcome and follow-up
The patient had an uneventful postoperative course; he left the hospital on POD 8; he was pain free and comfortable. At follow up, 6 and 15 months after surgery, he remained pain free and was able to return to his habitual job (taxi driver).
DISCUSSION
In present case report CRS-HIPEC was performed under PIOA-TAP perioperative based analgesia. Although PIOA is an established postoperative analgesic tool for major abdominal surgery it has not been previously reported in CRS-HIPEC, mainly because TEA was considered unbeatable due to adjustable duration, opioid sparing properties and powerful analgesic effects[16]. During CRS-HIPEC, heated intraperitoneal chemotherapy induces a hyperdynamic state characterised by increased heart rate and cardiac output with decreased systemic vascular resistance[7,17]; this condition may be present in the postoperative period for more than 48 hours[7]. Moderate to severe hypotension has been reported due to the addition of epidural analgesia induced sympathetic block to HIPEC induced vasodilation[5,7]. Due to this risk, some experienced centers prefer to restrict TEA to the postoperative period[6,18] or to begin epidural analgesia after the HIPEC phase, after assuring hemodynamic parameters are adequate[3]. In spite of the stated factors, others consider that TEA has a positive risk-profit ratio in CRS-HIPEC procedure[4,19,20].
In this context, spinal opioid analgesia offers several theoretical advantages. Preoperative intratechal opioid administration (PIOA) is a simpler technique, with minimal or absent hemodynamic effects[8]. As PIOA is performed in advance to surgery, subarachnoid opioids can start acting during the intraoperative period; PIOA had been reported to provide intraoperative analgesia[9,10] and opioid[9,10] and volatile anesthestic[10,14] sparing effects, in addition to the well known postoperative analgesic actions[9-13] .
The onset of PIOA depends of several factors, but three deserve special attention: The dermatomes involved in the surgical procedure[10-12,21,22], the liposolubility[11,21,22] of the opioids administered and its dose[11,12,22]. Martin-Larrauri et al.[10] compared the effect of 0,5 mg lumbar morphine PIOA on isoflurane requirement in three groups of patients. PIOA reduced isoflurane requirement compared with the same subcutaneous dose of morphine (control group); while patients in lumbar spine surgery group showed a significative isoflurane requirement reduction one hour after injection (due to the participation of caudal dermatomes), in the group of patients undergoing abdominal surgery, where more rostral dermatomes were involved, this effect was delayed (2,5 hours mean after PIOA); the accounted difference in morphine onset noted may represent the time needed to get sufficient morphine rostral diffusion to activate opioid receptors in the dorsal horn of thoracic spinal cord[11,21,22].
In the present case to bridge this analgesic gap (lumbar morphine subarachnoid injection-abdominal analgesia) we performed a bilateral oblique subcostal transversus abdominis plane (TAP) block[15] and we added a quick acting liposoluble opioid (fentany)[11,12,21,22] to intratechal morphine; so PIOA (morphine-fentanyl) + TAP block were combined to provide intra- and postoperative analgesia to this patient undergoing CRS-HIPEC.
As other performed interventions (pregabalin, acetaminophen, TAP block and subarachnoid fentanyl) are not sufficient per se to produce adequate perioperative analgesia for major abdominal surgery[10,15,20] intratechal morphine may be considered the cornerstone of the analgesic plan. The low liposolubility of morphine allows more rostral dermatome spread after lumbar injection and lower binding to lipid media and vascular absorption[11,12,20,21]. As morphine moves cephalad in the cerebrospinal fluid its concentration markedly decreases[11,21,22], so higher doses, for example than a cesarean section (0,1mg), are necessary to reach analgesic effects on rostral thoracoabdominal dermatomes (0,3-0,7mg)[11,12,21,22]. During skin incision, the values of heart rate, arterial tension and peripheral perfusion index did not show changes indicative of pain response, while the BIS values were consistent with adequate anesthetic depth, suggesting that TAP block + PIOA provided satisfactory analgesia. This patient did not require intraoperative IV opioids and he had reduced postoperative opioid consumption (total perioperative consumption morphine=6,65mg, fentanyl=29.3µg). This significantly differs of intraoperative (fentanyl 0,2-5,2mg)[1] and postoperative (morphine 7,06-212,9mg)[3] reported opioid consumption by other authors in CRS-HIPEC, strongly suggesting a perioperative opioid sparing effect. The total opioid dose may be of importance, as it has been suggested that opioid sparing techniques may improve bowel function in CRS-HIPEC[3] and reduce cancer relapse after CRS[20].
Previous studies suggest that CRS-HIPEC is an extremely painful procedure, and that these patients require longer TEA (mean 5-7 days) than other abdominal surgeries (mean 3 days)[1-4]. The accounted difference in pain intensity with other abdominal procedures is probably dependent on visceral and inner abdominal wall pain arising from scarring and chemical irritation. It was our working hypothesis that intratechal opioid analgesia would have a positive differential effect on visceral pain arising from HIPEC and that visceral analgesia would outlast the traditional 24-48 hours stated for subarachnoid morphine[11-13,21]. Although preliminary, this case report suggests that PIOA may be useful in preventing intense visceral pain as resulting from HIPEC .
Perioperative pain management in CRS-HIPEC is still an unsolved problem[2]. Hemodynamic stability, lack of additional intraoperative opioid administration, low postoperative pain scores and minimal opioid consumption suggest that the present analgesic plan may be an useful analgesic tool. It can be taken into consideration when TEA is contraindicated, after unsuccessful epidural catheter placement, or when it is valuable to avoid epidural analgesia-induced sympathetic blockade.
Further studies are necessary to establish if PIOA combined with bilateral oblique TAP block represents a simple and effective option to provide perioperative analgesia in CRS-HIPEC and in other major open abdominal surgeries.
CONCLUSION
Single shot subarachnoid opioids combined with a wall block can be an useful analgesic option when TEA is contraindicated, after unsuccessful epidural catheter placement, or when it is valuable to avoid epidural-induced sympathetic blockade in major abdominal surgery.
ACKNOWLEDGEMENTS
The author would like to thank Ignacio Raffa, MD (Staff Surgeon), Andrea Leticia Ascitelli, MD (Anesthesia Resident) and Daniel Esperatti (Nurse Anesthesist) for their help in the intraoperative care of the patient, to Yrma Patrone (Librarian), Asociación de Anestesia, Analgesia y Reanimación de Buenos Aires, for her dedicated assistance and to Oscar Martínez, for his technical support with the BIS equipment during the procedure.
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. Figure 1. Intraoperative image. The surgeons are finishing the last details to proceed with the hyperthermic intraperitoneal chemotherapy by using the open “coliseum technique”. Note the extensive xiphoid to pubis incision. The incoming and outcoming tubes can be observed. During the chemotherapy intraperitoneal temperature is continuously measured to keep it between 41-42°C; at the top of the photograph can be seen the temperature probe, not positioned yet. This image has been obtained from the anesthesiologist point of view so that the legs appear at the top.