Pain after Interventional Radiology in Oncology: A Case-Control Study from a 5-Year Cohort.

Background: Interventional radiology plays a major role in oncology both for curative and palliative treatment, but few reports address post-procedural pain. The purpose of this study was to quantify postoperative pain after interventional radiology procedures in oncology and to identify major pain-associated pre and intraoperative factors. Methods: From 2015 to 2019, all patients treated with interventional radiology were included retrospectively in a cohort study. Anesthetic protocols were standardized by the type of radiological procedure. Demographic data, preoperative treatments, analgesic agents, pain score levels, and morphine consumption from the post-anesthesia care unit (PACU) to hospital discharge were collected from databases. In an additional case-control study, patients reporting strong or intolerable pain in PACU were compared to those with no pain. Matching to control cases was based on the type of intervention, sex, and age. Results: From 4411 procedures, severe pain in PACU was more frequent in women (p < 0.04) and the youngest patients (p < 0.0001), after general anesthesia (p < 0.0001). Higher pain levels were associated with certain procedures, such as arterial embolization, limb cementoplasty, osteosynthesis, and abdominal tumor ablation, and when the intervention duration exceeded 160 min (p = 0.038). In the cohort study, high-dose remifentanil (≥0.055 µg/kg/min) was a risk factor for post-procedural high pain levels (p < 0.001). Intraoperative ketoprofen was associated with a decrease in high pain level incidence (p < 0.0001). Severe pain in PACU was a risk factor for severe pain in wards from day 0 until discharge. Conclusion: Severe pain depends on the type and duration of interventional radiology, type of anesthesia, and preoperative use of opiates. Limiting doses of remifentanil and injecting intraoperative analgesics, especially ketoprofen, may reduce the incidence of post-intervention severe pain.

End-Tidal Carbon Dioxide Pressure Measurement after Prolonged Inspiratory Time Gives a Good Estimation of the Arterial Carbon Dioxide Pressure in Mechanically Ventilated Patients.

BACKGROUND: End-tidal carbon dioxide pressure (PetCO2) is unreliable for monitoring PaCO2 in several conditions because of the unpredictable value of the PaCO2-PetCO2 gradient. We hypothesised that increasing both the end-inspiratory pause and the expiratory time would reduce this gradient in patients ventilated for COVID-19 with Acute Respiratory Distress Syndrome and in patients anaesthetised for surgery. METHODS: On the occasion of an arterial blood gas sample, an extension in inspiratory pause was carried out either by recruitment manoeuvre or by extending the end-inspiratory pause to 10 s. The end-expired PCO2 was measured (expiratory time: 4 s) after this manoeuvre (PACO2) in comparison with the PetCO2 measured by the monitor. We analysed 67 Δ(a-et)CO2, Δ(a-A)CO2 pairs for 7 patients in the COVID group and for 27 patients in the anaesthesia group. Results are expressed as mean ± standard deviation. RESULTS: Prolongation of the inspiratory pause significantly reduced PaCO2-PetCO2 gradients from 11 ± 5.7 and 5.7 ± 3.4 mm Hg (p < 0.001) to PaCO2-PACO2 gradients of -1.2 ± 3.3 (p = 0.043) and -1.9 ± 3.3 mm Hg (p < 0.003) in the COVID and anaesthesia groups, respectively. In the COVID group, PACO2 showed the lowest dispersion (-7 to +6 mm Hg) and better correlation with PaCO2 (R2 = 0.92). The PACO2 had a sensitivity of 0.81 and a specificity of 0.93 for identifying hypercapnic patients (PaCO2 > 50 mm Hg). CONCLUSIONS: Measuring end-tidal PCO2 after prolonged inspiratory time reduced the PaCO2-PetCO2 gradient to the point of obtaining values close to PaCO2. This measure identified hypercapnic patients in both intensive care and during anaesthesia.

Paraspinous Quadratus Lumborum Block: A New Analgesic Option for a Thigh Sarcoma Resection With Reconstruction-A Case Report.

Efficient pain management is essential for postoperative rehabilitation in patients undergoing a tumor resection with an immediate reconstructive surgery. Ultrasound-guided quadratus lumborum block has been described for abdominal or hip surgery, but not for concomitant surgery in the abdomen and the thigh. The paraspinous transmuscular approach has easy landmarks to perform this block. We present a case of a patient undergoing a resection of a sarcoma in the lower limb with an immediate reconstruction with a pedicled vertical designed deep inferior epigastric perforator flap, in whom a successful paraspinous transmuscular quadratus lumborum block for postoperative analgesia was performed.

Cancer surgery during the COVID-19 pandemic: The experience of a comprehensive cancer center performing preoperative screening by RT-PCR and chest CT scan.

BACKGROUND AND OBJECTIVES: During the worldwide pandemic of coronavirus disease 2019 (COVID-19), oncological procedures considered to be urgent could not be delayed, and a specific procedure was required to continue surgical activity. The objective was to assess the efficacy of our preoperative screening algorithm. METHODS: This observational retrospective study was performed between the 25th of March and the 12th of May 2020 in a comprehensive cancer center in France. Patients undergoing elective oncologic surgery were tested by preoperative nasopharyngeal reverse-transcription polymerase chain reaction (RT-PCR) that could be associated with a chest computerized tomography (CT) scan. RESULTS: Of the 510 screening tests (in 477 patients), only 5% (15/477) were positive for COVID-19 in 24 patients (18 RT-PCR+ and 7 CT scan+/RT-PCR-). Four patients were ultimately false positives based on the CT scan. In total, only 4.2% (20/477) of the patients were COVID-19+. The positivity rate decreased with time after the containment measures were implemented (from 7.4% to 0.8%). In the COVID-19+ group, 20% of the patients had postoperative pulmonary complications, whereas this was the case for 5% of the patients in the COVID-19 group. CONCLUSIONS: Maintaining secure surgical activity is achievable and paramount in oncology care, even during the COVID-19 pandemic, with appropriate screening based on preoperative RT-PCR.

The Opiorphin Analog STR-324 Decreases Sensory Hypersensitivity in a Rat Model of Neuropathic Pain.

BACKGROUND: Neuropathic pain represents a therapeutic challenge, and treatments with increased efficacy and tolerability still need to be developed. Opiorphin protects endogenous enkephalins from degradation, potentiating enkephalin-dependent analgesia via the activation of opioid pathways. Enkephalins are natural ligands of opioid receptors, with strong affinity for δ-opioid receptors. Expression of functional δ-opioid receptors increases in sensory neurons after peripheral nerve injury in neuropathic pain models. In a postoperative pain model, opiorphin and its stable analog STR-324 have an analgesic potency comparable to that of morphine, but without adverse opioid-related side effects. Consequently, administration of endogenous opiorphin peptides or STR-324 might be effective in managing peripheral neuropathic pain. METHODS: In this study, STR-324 was administered intravenously over the course of 7 days to rats with mononeuropathy induced by L5-L6 spinal nerve root ligation. The rats exhibited mechanical allodynia, thermal hyperalgesia, and spontaneous pain-related behavior throughout the testing period. RESULTS: Here, we report that the continuous administration of STR-324 significantly reduced mechanical allodynia and spontaneous pain-related behavior from day 2 to day 7 in animals that received 10 or 50 µg/h of STR-324 as compared to placebo-treated animals (P < .00001 and P < .0011, respectively, for mechanical allodynia; P = .028 and P = .0049, respectively, for spontaneous pain-related behavior). In addition, STR-324 reduced the pain-evoked expression of spinal c-Fos in this model, demonstrating that it acts at least in part through inhibition of endogenous nociceptive pathways. CONCLUSIONS: These observations suggested that STR-324 may be an effective addition to the multimodal approach for treating clinical neuropathic pain.

STR-324, a Stable Analog of Opiorphin, Causes Analgesia in Postoperative Pain by Activating Endogenous Opioid Receptor-dependent Pathways.

BACKGROUND: Opiorphin is a naturally occurring potent analgesic human peptide. It protects enkephalins from degradation and inhibits pain perception in various acute pain models via activation of endogenous opioid pathways. However, the efficacy of opiorphin continuous infusion and its chemically stable form, STR-324, in postoperative pain is unknown. METHODS: Using the Brennan model of plantar incision-induced hypersensitivity, the authors examined the postsurgical analgesic response to mechanical and thermal stimuli of 7-day continuously intravenously infused drugs (8 to 10 rats per group). Antinociception from opiorphin with reference to morphine and STR-324 was assessed. Spinal c-Fos expression and the involvement of opioid receptor-dependent pathways were investigated. The occurrence of respiratory and hemodynamic adverse effects of opiorphin was also tested. RESULTS: Intravenous infusion of opiorphin significantly reduced responses to mechanical stimuli from days 1 to 4 post surgical period at 143 to 175-kPa mean ranges compared with 23 to 30-kPa mean ranges for vehicle (P < 0.05). During the 3-day postoperative period, no respiratory rate, oxygen saturation, arterial pressure, or heart rate adverse effects were induced by opiorphin. STR-324 consistently inhibited mechanical and thermal hyperalgesia with similar potency as that of opiorphin. Mechanistic analyses demonstrated that the STR-324 antinociceptive effect was reversed by the opioid antagonist, naloxone. Also, STR-324 significantly reduced the number of pain-evoked spinal cFos-immunoreactive nuclei. CONCLUSION: Intravenous infusion of opiorphin and STR-324 produced significant antinociceptive effect in a postoperative pain model. This study demonstrates that STR-324 is effective in postoperative pain management due to its strong antihyperalgesic effects mediated via opioid-dependent antinociceptive pathways. Opiorphin analog should represent a new class of potent and safe analgesics.

The median effective dose of ketamine and gabapentin in opioid-induced hyperalgesia in rats: an isobolographic analysis of their interaction.

BACKGROUND: Ketamine and gabapentin have been shown to prevent the delayed hyperalgesia induced by short-term use of systemic opioids. The mechanism of this action is believed to be likely at the spinal level, through an antagonism of the N-methyl-D-aspartate receptors for ketamine, and through a specific binding site for gabapentin. In this study, we sought to determine the nature of the interaction of these 2 mechanistically distinct antihyperalgesic drugs in a model of opioid-induced hyperalgesia in rats. The median effective antihyperalgesic doses of each drug and of their combination were first defined, to assess the nature of the interaction using an isobolographic analysis. METHODS: Long-lasting hyperalgesia was induced in male Sprague Dawley rats with subcutaneous fentanyl (4 injections, 60 µg/kg per injection at 15-minute intervals) resulting in a total dose of 240 µg/kg. Subcutaneous ketamine, or intraperitoneal gabapentin, or their combination was administered 30 minutes before the first subcutaneous fentanyl injection. Sensitivity to nociceptive stimuli (von Frey filaments) was assessed on the day of the experiment and on the day after injections. The dose of ketamine and gabapentin received by a particular animal was determined by the response of the previous animal of the same group, using an up-and-down technique. Initial doses were 10 mg/kg and 300 mg/kg, with dose adjustment intervals of 1 mg/kg and 30 mg/kg, in the ketamine and gabapentin groups, respectively. The initial doses of ketamine and gabapentin were 5 mg/kg and 150 mg/kg, respectively, in the ketamine-gabapentin group, with the same dose adjustment intervals. Antihyperalgesic efficacy was defined as complete prevention of hyperalgesia on the day after drug injections. RESULTS: The median effective antihyperalgesic doses (median value and 95% confidence interval) of ketamine and gabapentin were 12.4 mg/kg (11.7-13.1 mg/kg) and 296.3 mg/kg (283.5-309.1 mg/kg), respectively. The median effective antihyperalgesic dose of the combination was 4.3 mg/kg (3.7-4.6 mg/kg) for ketamine and 123.9 mg/kg (111.1-136.7 mg/kg) for gabapentin. CONCLUSION: The isobolographic analysis demonstrated that the combination of the 2 drugs produces effective antihyperalgesia with a supraadditive (synergistic) action.

Intraoperative ultrasonography during percutaneous Achilles tendon repair.

BACKGROUND: The purpose of the study was to determine whether real-time intraoperative ultrasonography improved implant positioning and stump approximation in patients with acute Achilles tendon rupture managed percutaneously. MATERIALS AND METHODS: The needles were introduced percutaneously without ultrasonography and their position was checked relative to cutaneous landmarks and by palpation. Then, intraoperative ultrasonography was performed to assess needle position at the proximal tendon segment, tendon tear, and distal tendon segment. Incorrectly placed needles were removed and reinserted under real-time ultrasonographic guidance. Tendon apposition was checked ultrasonographically. RESULTS: We included 21 patients (19 males, two females) with unilateral acute Achilles tendon rupture, in whom 42 needles (one medial and one lateral) were inserted. Correct positioning was achieved without ultrasonographic guidance for 19 (45%) needles overall, 15 of 21 (71%) medial needles, and four of 21 (19%) lateral needles. The remaining 23 needles were correctly repositioned under ultrasonographic guidance. The correct positioning rates with and without ultrasonography differed significantly for all needles (p < 0.0001) and for lateral needles (p < 0.0001) but not for medial needles (p = 0.03). Intraoperative ultrasonography confirmed tendon stump approximation in all cases. CONCLUSION: Without imaging, 55% of needles were correctly positioned. Intraoperative ultrasonography allowed correct positioning of all needles and provided intraoperative confirmation of stump approximation.

Gabapentin prevents delayed and long-lasting hyperalgesia induced by fentanyl in rats.

BACKGROUND: Opioid-induced hyperalgesia can develop rapidly after opioid exposure. Neuropathic pain and opioid-induced hyperalgesia share common pathophysiologic mechanisms. Gabapentin is effective for the management of neuropathic pain and may therefore prevent opioid-induced hyperalgesia. This study tested the effectiveness of gabapentin for prevention of long-lasting hyperalgesia induced by acute systemic fentanyl in uninjured rats. Involvement of the alpha2delta auxiliary subunits of voltage-gated calcium channels in the prevention of opioid-induced hyperalgesia by gabapentin also was assessed. METHODS: Hyperalgesia was induced in male Sprague-Dawley rats with subcutaneous fentanyl (four injections, 20, 60, or 100 microg/kg per injection at 15-min intervals). Intraperitoneal (30, 75, 150, or 300 mg/kg) or intrathecal (300 microg) gabapentin was administered 30 min before or 300 min after (intraperitoneal 150 mg/kg) the first fentanyl injection. Sensitivity to nociceptive stimuli (paw-pressure test) was assessed on the day of the experiment and for several days after injections. The effects combining gabapentin with intrathecal ruthenium red (20 ng) also were assessed. RESULTS: Fentanyl administration was followed by an early increase (analgesia) and by a later and sustained decrease (hyperalgesia) in nociceptive thresholds. Gabapentin did not significantly modify the early analgesic component but dose-dependently prevented the delayed decrease in nociceptive threshold. Ruthenium red partially, but significantly, opposed the prevention of opioid-induced hyperalgesia by gabapentin. CONCLUSIONS: Intraperitoneal and intrathecal gabapentin prevents the development of hyperalgesia induced by acute systemic exposure to opioids. This prevention may result, at least in part, from binding of gabapentin to the alpha2delta auxiliary subunits of voltage-gated calcium channels.

Protective effect of prior administration of magnesium on delayed hyperalgesia induced by fentanyl in rats.

PURPOSE: Magnesium exerts a physiological block of the ion channel on the N-methyl-D-aspartate receptor, and may therefore prevent the induction of central sensitization. The purpose of this study was to assess whether systemic magnesium can prevent long-lasting hyperalgesia induced by sc fentanyl administration in uninjured rats. METHODS: Long-lasting hyperalgesia was induced in male Sprague Dawley rats with sc fentanyl (four injections, 60 microg x kg(-1) per injection at 15-min intervals). Magnesium sulphate (100 mg x kg(-1)) was injected ip 30 min prior to the first sc fentanyl injection. Sensitivity to nociceptive stimuli (paw-pressure test) was assessed for several days after injections. RESULTS: Subcutaneous fentanyl led to delayed hyperalgesia associated with a decrease in the nociceptive threshold lasting two days (35% decrease for the maximum effect). Intraperitoneal magnesium sulphate partially but significantly (P < 0.05) prevented the delayed decrease in the nociceptive threshold following sc administration of fentanyl. CONCLUSIONS: This study shows that magnesium may prevent the delayed and prolonged hyperalgesia following fentanyl administration in rats.

A single dose of intrathecal morphine in rats induces long-lasting hyperalgesia: the protective effect of prior administration of ketamine.

An active pronociceptive process involving N-methyl-D-aspartate (NMDA) receptor activation is initiated by opioid administration, leading to opioid-induced pain sensitivity. Experimental observations in rats have reported reduction of baseline nociceptive threshold after prolonged spinal opioid administration. In this study we sought to determine whether a single dose of intrathecal morphine can induce hyperalgesia in uninjured rats and to assess the effects of pretreatment with the NMDA-antagonist ketamine on nociceptive thresholds. Sensitivity to nociceptive stimuli (paw pressure test) was assessed for several days after an acute intrathecal injection of morphine (5 microg and 10 microg) in male Sprague-Dawley rats. The effects of subcutaneously administered NMDA-receptor antagonist ketamine (10 mg/kg) before intrathecally administered morphine were also evaluated. A single intrathecal injection of morphine led to a biphasic effect on nociception; early analgesia associated with an increase in the nociceptive threshold lasting 3-5 h was followed by delayed hyperalgesia associated with a decrease in the nociceptive threshold lasting 1-2 days. Subcutaneous ketamine did not significantly modify the early analgesic component but almost completely prevented the delayed decrease in nociceptive threshold after intrathecal administration of morphine. A single intrathecal injection of morphine in rats produces a delayed and sustained hyperalgesia linked to the development of opioid-induced pain sensitivity.