Comparison of Caudal Block vs. Penile Block vs. Intravenous Fentanyl Only in Children Undergoing Penile Surgery: A Prospective, Randomized, Double Blind Study.

Objectives: Penile surgery is commonly performed in pediatric surgical centers. There is no consensus regarding which analgesic method is most effective in controlling pain in these children. Methods: Consecutive children between 4 months and 16 years of age who underwent elective penile surgery were recruited. After inhaled induction of anesthesia, children were randomized to one of three methods of intraoperative analgesia: caudal block, IV fentanyl titrated to surgical response and spontaneous respiration, or dorsal penile nerve block (DPNB). All patients were given inhaled agents; fentanyl was added if either block was insufficient. Demographic data, analgesic use and pain scores were recorded by a blinded investigator in the PACU and ward. Pain scores, analgesic requirement, and recovery parameters of returning to normal activity level, eating, and voiding post-operatively for up to 4 days, were compared. Results: 116 children were recruited. Pain scores in the post anesthesia care unit were significantly lower in the DPNB and caudal block groups compared to the fentanyl group for the first 30 postoperative min. Pain scores and analgesic use were subsequently similar among the three groups for the rest of the study period. There was no statistical difference in time to eat, return to normal activity or in parental satisfaction scores among the groups. There was a trend toward earliest time to void in the DPNB group. Conclusions: Regional blocks most effectively controlled pain for 30 min after surgery. The choice of intra-operative analgesia protocol had no effect on later pain and recovery parameters.

Perspectives of Ketamine Use in COVID-19 Patients.

Hospitalized coronavirus disease 2019 (COVID-19)-infected patients suffer from both physical impairments and mental stress. Respiratory insufficiency and cardiovascular disturbances require most of the intensive care interventions, but they are also accompanied by depressive conditions, sadness and fear of dying. Sedatives are mostly respiratory and cardiovascular depressants and do not provide resistance to the pro-inflammatory burst induced by the virus. Ketamine is a unique and safe drug that enables well-controlled sedation and anesthesia, attenuates depression and mitigates suicidal thoughts, without depressing respiratory or cardiovascular mechanics. This brief communication highlights the benefits potentially provided by ketamine to patients hospitalized for COVID-19 infection.

Ultrasonographic Assessment of Bladder Volumes in Children Undergoing Penile Surgery: Does the Type of Anesthesia Matter?

BACKGROUND: There are scant data reporting postoperative ultrasonographically measured bladder volumes in children undergoing penile surgery. STUDY QUESTION: We studied the effect of various anesthesia techniques on return of micturition after penile surgery in children, using ultrasonographically measured bladder volumes. DATA SOURCES: Ultrasonographically measured postvoiding residual bladder volumes indexed to age-appropriate capacity, and time elapsed between the end of surgery and spontaneous voiding after pediatric circumcision, distal hypospadias repair, or repair of urethrocutaneous fistula, were studied. STUDY DESIGN: Children between 4 months and 12 years were randomized to caudal block, intravenous (IV) fentanyl or penile block, in association with inhaled general anesthesia. Bladder volumes were measured before surgery and immediately after voiding for the first time. Time to first postsurgery void was also recorded. RESULTS: Thirty-one children completed all assessments; 12 underwent caudal block, 9 IV fentanyl anesthesia, and 7 were given penile block. The mean first postvoid bladder residual volumes were highest in the caudal and lowest in the penile block children (27.5 vs. 17.3 mL, P = 0.003). The time elapsing between the end of surgery and first voiding was the longest in the fentanyl group compared with caudal and penile blocks (232, 178, 150 minutes, respectively, P = 0.02). CONCLUSIONS: None of the anesthetic techniques provoked postoperative urinary retention after minor penile surgery in children. The penile block appears superior to caudal block or to IV fentanyl-based anesthesia with regard to postoperative recovery of normal micturition.

Postoperative hyperalgesia-A clinically applicable narrative review.

Postoperative hyperalgesia (POH) is a condition characterized by signs and symptoms of pain despite the provision of conventional analgesia. In most cases, anesthesiologists are called upon soon after surgery, but occasionally it may occur as a late event. Persistent uncontrolled pain may transform into chronic or neuropathic pain. Correct diagnosis of POH is essential since similar phenomenon may exacerbate if misdiagnosed, while proper treatment is frequently achievable by pharmacological remedies. This review will describe the causes for POH and its bio-neuro-pharmacological basis, and clinical symptoms and signs directing the physician towards correct diagnosis of this paradoxical condition of pain, as well as modes capable of preventing POH from occurring. The pharmacological approach upon suspecting or diagnosing POH will focus on the use of anesthetic and non-anesthetic drugs that attenuate nociceptive- and opioid-induced paradoxical pain, and non-opioid adjuvant drugs, among which are ketamine or gabapentinoids, the two notably compounds that antagonize abnormal central sensitization that is at the basis of POH.

Perioperative pregabalin for reducing pain, analgesic consumption, and anxiety and enhancing sleep quality in elective neurosurgical patients: a prospective, randomized, double-blind, and controlled clinical study.

OBJECTIVE The aim of this study was to assess in-hospital (immediate) postoperative pain scores and analgesic consumption (primary goals) and preoperative anxiety and sleep quality (secondary goals) in patients who underwent craniotomy and were treated with pregabalin (PGL). Whenever possible, out-of-hospital pain scores and analgesics usage data were obtained as well. METHODS This prospective, randomized, double-blind and controlled study was conducted in consenting patients who underwent elective craniotomy for brain tumor resection at Tel Aviv Medical Center between 2012 and 2014. Patients received either 150 mg PGL (n = 50) or 500 mg starch (placebo; n = 50) on the evening before surgery, 1.5 hours before surgery, and twice daily for 72 hours following surgery. All patients spent the night before surgery in the hospital, and no other premedication was administered. Opioids and nonsteroidal antiinflammatory drugs were used for pain, which was self-rated by means of a numerical rating scale (score range 0-10). RESULTS Eighty-eight patients completed the study. Data on the American Society of Anesthesiologists class, age, body weight, duration of surgery, and intraoperative drugs were similar for both groups. The pain scores during postoperative Days 0 to 2 were significantly lower in the PGL group than in the placebo group (p < 0.01). Analgesic consumption was also lower in the PGL group, both immediately and 1 month after surgery. There were fewer requests for antiemetics in the PGL group, and the rate of postoperative nausea and vomiting was lower. The preoperative anxiety level and the quality of sleep were significantly better in the PGL group (p < 0.01). There were no PGL-associated major adverse events. CONCLUSIONS Perioperative use of twice-daily 150 mg pregabalin attenuates preoperative anxiety, improves sleep quality, and reduces postoperative pain scores and analgesic usage without increasing the rate of adverse effects. Clinical trial registration no.: NCT01612832 ( clinicaltrials.gov ).

Protective effects of rosuvastatin in a rat model of lung contusion: Stimulation of the cyclooxygenase 2-prostaglandin E-2 pathway.

BACKGROUND: Lung contusion, which can occur in patients with blunt thoracic trauma, is a leading risk factor for development of acute lung injury (ALI) and acute respiratory distress syndrome. Statins are lipid-lowering drugs with many beneficial antiinflammatory and antioxidative effects. We therefore hypothesized that the administration of statins immediately after trauma will inhibit the production of inflammatory mediators, and thereby alleviate the severity of lung injury. METHODS: A model of blunt chest injury in rat was employed. The effects of statins (rosuvastatin) and cyclooxygenase-2 (COX-2) inhibitors (meloxicam) on ALI were assessed by measuring inflammatory mediator levels in the serum and in the bronchoalveolar space. Animals were killed at the end of day 3. Histologic evaluation of lung tissue was performed to confirm the presence and severity of lung contusion as well as the effects of statins, nonsteroidal antiinflammatory drugs, and their combination. RESULTS: Administration of meloxicam after lung contusion decreased the amount of neutrophil infiltration; however, marked hemorrhage and edema were still noticed. Administration of rosuvastatin decreased significantly cytokine levels that were increased after the blunt chest trauma. Rosuvastatin increased the expression of inducible nitric oxide (iNOS), COX-2, heme oxygenase-1 (HO-1), and prostaglandin E2 (PGE-2) in the bronchoalveolar lavage fluid of the rat contused lungs. Coadministration of meloxicam prevented these changes. CONCLUSION: Rosuvastatin treatment after lung contusion attenuated several features of ALI. The enhanced activity of iNOS, COX-2, and HO-1 in the lung may reflect the advent of protective processes that took place in the contused lung. To our knowledge, this is the first demonstration that prostaglandin pathways play an essential role in the effects of statins in lung injury.

Patient-tailored combinations of systemic and topical preparations for localized peripheral neuropathic pain: a two-case report.

This report describes two patients with peripheral neuropathic pain (PNP): a 43-year-old man with upper leg PNP and a 75-year-old woman with post herpetic neuralgia of the perineum and vagina. Pain was inadequately managed in both patients for a long time. A patient-tailored approach, including a combination of systemic and topical compounds, required multiple adjustments for each patient before finally achieving adequate pain control. The first patient achieved pain control with a combination of systemically-administered drugs: dipyrone (1 g 3 times a day), pregabalin (300 mg twice a day), duloxetine (60 mg once daily in the morning), and dextromethorphan (60 mg 3 times/day), plus topical compounds (10% ketamine, 5% lidocaine, and 10% ketoprofen) in penetrating enhancing gel, and sublingual ketamine (10 mg) for breakthrough pain. The second patient achieved optimal pain control with dipyrone (500 mg three times per day), pregabalin (150 mg twice a day), dextromethorphan (60 mg three times per day), plus topical compounds (10% ketamine, 0.3% clonidine, 5% diclofenac) in a penetrating enhancing gel. Notably, the individualized approach described herein was made possible through collaboration between a public health pain specialist and a private sector compounding pharmacist, highlighting the importance of such infrequent but, highly desirable collaborations.

Pneumoperitoneum in the presence of acute and chronic kidney injury: an experimental model in rats.

PURPOSE: There is evidence that pneumoperitoneum induces transient changes in renal function in healthy individuals. Its effect on malfunctioning kidneys is not well known. We investigated effects caused by pneumoperitoneum in animals with impaired renal function. MATERIALS AND METHODS: Male Wistar rats underwent subtotal (5/6) nephrectomy in 2 sequential steps to induce renal failure. Two and 10 weeks postoperatively rats were classified with acute and chronic kidney injury, respectively. At those time points all rats were exposed to 0, 5 and 8 mm Hg pneumoperitoneum for 60 minutes. Changes in creatinine, blood urea nitrogen and creatinine clearance were measured. Histopathological changes and apoptosis were also evaluated in the subgroups. RESULTS: A total of 18 rats with acute and 18 with chronic kidney injury completed the study. Creatinine and blood urea nitrogen did not change after applying pneumoperitoneum in the different pressure subgroups but creatinine clearance significantly decreased in the 5 and 8 mm Hg subgroups in rats with acute and chronic kidney injury. Histopathological findings in the acute kidney injury subgroups that underwent 5 and 8 mm Hg pressure revealed ischemic changes while compensatory hypertrophy was noticed in the chronic injury pressurized subgroups. The apoptotic count was significantly higher in the chronic injury subgroups compared to their acute injury pressurized counterparts. CONCLUSIONS: Pneumoperitoneum seems feasible in rats with impaired baseline renal function. Particularly chronic cases should not be considered a contraindication to pneumoperitoneum while in acute cases pneumoperitoneum might be detrimental.

[Patient dissatisfaction following prolonged stay in the post-anesthesia care unit due to unavailable ward bed in a tertiary hospital].

OBJECTIVES: The present study aimed to evaluate subjective reactions of post-surgery and anesthesia patients who stay in post-anesthesia care units (PACU) longer than necessary medically, due to administrative causes. METHODS: We interviewed consenting postoperative patients during an 18-month period. All patients who remained in the PACU twice our obligatory PACU length of stay (> 4 hours) due to lack of an available bed in the appropriate hospital ward, were interviewed at the time of discharge. The study group consisted of those who remained > 4 hours after surgery and a control group of patients who were discharged within 4 hours. The questions were chosen from different sources, including generic and condition-specific questionnaires. RESULTS: A total of 67 patients stayed > 4 hours and 63 < 4 hours. The overall mean PACU length of stay for the former was 14.23 +/- 5.77 hours (range 1.5-30 hours). No significant differences were found between the groups in terms of age, gender, surgical time or postoperative pain visual analogue scale. Irritability due to lack of independence were statistically higher, and satisfaction rates were lower in patients who stayed > 12 hours compared to those who were discharged after 4-12 hours (P < 0.05). CONCLUSIONS: Overcrowded wards may lead to significant delays in discharge from the PACU. Prolonged stay in the PACU requires attention, both from the administrative and the medical standpoints, because it may irritate the patient. Patients' irate behavior may distract the medical staff from effectively performing their duties and interferes with optimal medical care in the PACU.

Low plasma C-reactive protein level as an early diagnostic tool for heatstroke vs central nervous system-associated infection in the ED.

PURPOSES: Heatstroke (HS) is a life-threatening condition, manifested by systemic inflammation and multiorgan failure. Rapid recognition and treatment are life saving. We report a laboratory-oriented characterization of HS by low plasma C-reactive protein (CRP) level and propose its usefulness in distinguishing this type of hyperpyrexia from central nervous system-associated high core temperature. METHODS: After institutional review board approval, records of patients admitted to general intensive care unit between August 2008 and September 2011 with core temperature 39.0°C or higher due to HS or meningoencephalitis (ME) were reviewed. Patients' demographics, CRP on admission and 24 to 48 hours later, serum creatinine, creatine phosphokinase, platelets count, international normalized ratio, alanine transaminase, serum pH, and lactate levels were retrieved. RESULTS: Thirty-six patients were admitted to the intensive care unit with high core temperature: 19 patients, aged 21 to 85 years, had HS; 17 individuals, aged 22 to 81 years, had ME. None of the HS individuals had infection. Twelve HS patients were previously healthy; in 13 patients, the event occurred postexercise. Mean admission CRP levels was 2.1 ± 3.3 mg/L in the HS group compared with 129 ± 84 mg/L in the ME patients (P < .0001); mean 24- to 48-hour CRP levels were 14.6 ± 16.8 vs 139 ± 98 mg/L, respectively (P < .0001). There were no clinically significant differences between the groups regarding laboratory parameters indicative of end-organ damage. Six HS patients underwent computed tomography and/or lumbar puncture before starting intensive cooling, due to misdiagnosis; 5 of them died subsequently. CONCLUSIONS: Low serum CRP levels characterize non-central nervous system-associated HS. This available laboratory test could identify noninfectious hyperthermic patients upon admission, saving precious time until treatment and avoiding unnecessary diagnostic tests.

Transanal endoscopic microsurgery for the resection of submucosal and retrorectal tumors.

BACKGROUND: Transanal endoscopic microsurgery (TEM) was originally designed for local endoscopic excision of benign and low-grade mucosal rectal lesions through an endoscopic system. The procedure is particularly challenging for submucosal and retrorectal lesions, as the tumor margins are not well defined. OBJECTIVE: To investigate patient and surgical characteristics of TEM as a treatment for submucosal rectal and retrorectal lesions. METHODS: All the patients in our department of general surgery who underwent TEM for a submucosal rectal or retrorectal lesion, between the years 2001 and 2011, were identified. Their charts were reviewed and data pertaining to demographic characteristics and medical history, including tumor characteristics, were collected. Operative notes and histopathology reports were also reviewed. The adequacy of the tumor resection, that ism attainment of free margins, endoscopic completion of the procedure, and perioperative complications, were assessed. RESULTS: Fifteen patients (5 females, 10 males), mean age 53.9 ± 16.9 years, were identified. The main indications for surgery were gastrointestinal stromal tumor (5 patients) and tailgut or duplication cyst (4 patients). All procedures were completed endoscopically. The median distance from the anal verge was 7.3 cm (range, 5 to 10 cm), and the mean diameter of the tumors was 3 ± 1.1 cm. The one patient in whom the margins presented tumoral involvement underwent repeated TEM. No intraoperative complications were reported. The postoperative complication rate was 13.3%, and the mean length of hospital stay was 1.85 ± 1.77 days. CONCLUSIONS: TEM for retrorectal and submucosal rectal lesions is feasible and safe. A remarkably low morbidity rate and limited surgical injury favor TEM in selected patients.

Assessment of the clinical usefulness of imaging modalities in identifying postoperative upper gastrointestinal tract leaks requiring reoperation.

PURPOSE: To assess the usefulness of imaging modalities in the diagnosis and determination of whether postoperative upper gastrointestinal tract leak (UGITL) requires operative intervention. METHODS: : Patients with suspected UGITL who underwent reoperation ≤ 30 days after the primary operation with intraoperative confirmation of leaks were identified. Data of those patients who had undergone computerized tomography (CT) or upper gastrointestinal contrast study (UGIS) before reoperation were reviewed. The usefulness and impact of imaging studies obtained before reoperation were evaluated. RESULTS: Thirty patients with confirmed UGITL were identified, 24 of whom had undergone imaging studies before reoperation. Fourteen CTs (63.7%) and 4 UGIS (67%) were positive or highly indicative of UGITL. The interval between the primary operation and the reoperation and the morbidity rates after the reoperation were similar between patients with and those without imaging studies before the reoperation (5.6 ± 4.8 vs. 6.8 ± 4.2 d, P=0.55; 91.6% vs. 100%, P=0.29, respectively). False-negative imaging results caused postponement of reoperation by ≥ 24 hours in 4 patients whose outcome was similar to those with true-positive results. CONCLUSIONS: CTs and UGIS are supportive tools when deciding whether to reoperate for postoperative UGITL. However, a negative imaging study for UGITL does not exclude it definitively, and therefore should not replace clinical evaluations.

Morphine at "sub-analgesic" background infusion rate plus low-dose PCA bolus control pain better and is as safe as twice a bolus-only PCA regimen: a randomized, double blind study.

Morphine for postoperative pain control is commonly titrated via intravenous patient-controlled analgesia (IV-PCA). An IV morphine background infusion is rarely used. We investigated whether analgesia is effectively attained and morphine consumption is reduced if PCA titration is coadjuvated by a continuous infusion protocol. Following colorectal cancer surgery, consenting patients were randomized to receive a minimal ("sub-analgesic") dose of morphine 0.01 mg/kg/h background infusion plus a 0.01 mg/kg bolus (BI), or a 1.5mg bolus-only morphine (B0) (bolus ratio ∼1:2). Bolus lockout time was 7 min in either case. All patients received 0.1mg/kg morphine before protocol initiation, and diclofenac 75 mg intramuscularly b.i.d. during the study period, lasting 48 h. Eighty-six patients (51 males, age 26-95 years) participated in the study. The total mean morphine consumption during the 48 h was 25% lower in the BI than in the B0 group (P<0.05). Although the former applied the PCA device for boluses 19% less than the latter (P<0.05), their pain score was lower (P<0.05) most of the time, and they reported greater satisfaction (P<0.05) on a 10-scale numerical rating score. Pre- and postoperative vital signs were similar for both groups. No patient depicted hypoxemia or lapsed into deep sedation. Four BI and three B0 patients required treatment for postoperative nausea and vomiting. One BI patient had transient pruritus and one B0 69-year individual became disoriented 24h into treatment; either event subsided soon after stopping their respective regimen without the need for treatment. The main conclusions of the results are that very-low-dose background morphine infusion combined with small-dose PCA boluses may provide better pain relief, lower morphine consumption, and minimal complication rate as a 1.5mg PCA bolus-only protocol.

The hepatorenal reflex contributes to the induction of oliguria during pneumoperitoneum in the rat.

BACKGROUND: Hepatic blood flow is known to decrease during pneumoperitoneum. Studies have shown that such changes affect kidney urinary output through the sympathetic pathway known as the hepatorenal reflex. This study investigated the potential role of the hepatorenal reflex in pneumoperitoneum-induced oliguria. The authors hypothesized that oliguria detectable during pneumoperitoneum is caused by activation of the hepatorenal reflex. METHODS: Denervation of the sympathetic nervous structure was performed in 15 rats by applying 1 ml of 90 % aqueous phenol solution circumferentially to the portal vein and vena cava area at their entrance to the liver. The same was applied to only the peritoneum in 15 nondenervated rats. After 2 weeks, the rats were divided into three subgroups (5 rats per subgroup) that were exposed respectively to carbon dioxide-induced pneumoperitoneum at 0, 10, and 15 mmHg for 2 h. Statistical analysis was performed using Student's t test and analyses of variance. RESULTS: Denervation did not affect the preinsufflation parameters. The denervated and the nondenervated 0-mmHg subgroups presented with similar parameters. The postinsufflation mean urine output was significantly lower in the nondenervated than in the denervated 10- and 15-mmHg subgroups (p = 0.0097). The denervated rats had a final creatinine clearance 29 % lower than the preinsufflation value (p = 0.83), whereas the nondenervated animals presented a 79 % drop in creatinine clearance (p = 0.02). CONCLUSION: The study findings indicate that the hepatorenal reflex plays an important role in the pathophysiology of oliguria that occurs during pneumoperitoneum in the rat.

Non-opioid IV adjuvants in the perioperative period: pharmacological and clinical aspects of ketamine and gabapentinoids.

Untreated acute postoperative pain can transform into chronic pain that may have major negative effects on the individual's quality of life. It can also prolong recovery, rehabilitation and length of hospital stay, thus affecting societal economic burden. Given the multiplicity of mechanisms involved in postoperative pain, a multimodal analgesia regimen, using a combination of opioids and multiple agents aiming to augment their effects via different routes of administration, is a pharmacologically appropriate approach. This polypharmacological application provides superior pain relief at rest and after movement, reduced opioid consumption associated with reduced analgesic-related adverse effects, and better chances to prevent the induction of later hyperalgesia. The most important adjuncts currently employed are ketamine and gabapentinoids. They have been shown to help in reaching the desired effect when administered at drug-specific modes and at proven effective dosing throughout the perioperative period.

Changes in end-tidal carbon dioxide due to gastric perforation during pneumoperitoneum in the rat.

BACKGROUND: Carbon dioxide is the most widely used gas to establish pneumoperitoneum during laparoscopic surgery. Gastrointestinal trauma may occur during the peritoneal insufflation or during the operative phase itself. Early diagnosis of these injuries is critical. OBJECTIVES: To assess changes in end-tidal carbon dioxide (ETCO2) following gastric perforation during pneumoperitoneum in the rat. METHODS: Wistar rats were anesthetized, tracheotomized and mechanically ventilated with fixed minute volume. Each animal underwent a 1 cm abdominal longitudinal incision. A 0.3 x 0.3 cm cross-incision of the stomach was performed in the perforation group but not in the controls (n = 10/group) and the abdomen was closed in both groups. After stabilization, CO2-induced pneumoperitoneum was established at 0, 5, 8 and 12 mmHg for 20 min periods consecutively, each followed by complete pressure relief for 5 min. RESULTS: Ventilatory pressure increased in both groups when pneumoperitoneal pressure 5 mmHg was applied, but more so in the perforated stomach group (P = 0.003). ETCO2 increased in both groups during the experiment, but less so in the perforated group (P = 0.04). It then returned to near baseline values during pressure annulation in all perforated animals but only following the 0 and 5 mmHg periods in the controls. CONCLUSIONS: When subjected to pneumoperitoneum, ETCO2 was lower in rats with a perforated stomach than in those with an intact stomach. An abrupt decrease in ETCO2 during laparoscopy may signal gastric perforation.

Oxidants as important determinants of renal apoptosis during pneumoperitoneum: a study in an isolated perfused rat kidney model.

INTRODUCTION: Pneumoperitoneum-associated ischemia-reperfusion (IR) may initiate renal dysfunction. Whether oxidants are responsible for renal structural damage, such as cell apoptosis, has not yet been evaluated. We investigated such eventuality in an isolated rat kidney model. METHODS: Thirty-five rat kidneys with their vessels and ureter were harvested and perfused within a closed environment at flow of 15 ml min(-1). After stabilization, kidneys were assigned to one of five groups (n = 7 per group): CO(2)-induced intrachamber pressure of 8, 12, or 0 mmHg (control), and 8 or 12 mmHg pressure applied to kidneys from rats treated pre-experimentally with tungsten for 14 days. Pressurization lasted 60 min. RESULTS: Organ perfusion pressure raised as intrachamber pressure increased. Urinary output decreased in the two pressurized nonpretreated groups. Intrachamber pressure was directly associated with an increase in postexperimental xanthine oxidase tissue levels. Twofold apoptosis was documented (p < 0.05) in cortex of nonpretreated kidney in the 12 mmHg group compared with the 8 or 0 mmHg groups. Tungsten pretreatment significantly (p < 0.05) attenuated the abnormalities documented in the 12 mmHg group, but less so in the 8 mmHg pressurized nontreated counterparts. CONCLUSIONS: Pneumoperitoneal pressure applied to isolated perfused kidney is associated with renal apoptosis. This rapidly induced structural renal damage is oxidant dependent and can be attenuated by antioxidants. Further studies may shed more light on the role of antioxidants in preventing pneumoperitoneum-induced kidney dysfunction.

Repeated and escalating preoperative subanesthetic doses of ketamine for postoperative pain control in patients undergoing tumor resection: a randomized, placebo-controlled, double-blind trial.

BACKGROUND: Ketamine induces a short-term effect on postoperative pain when administered intravenously immediately before or during acute pain. Repeated administration of low-dose ketamine may induce long-term pain relief in chronic pain syndromes. OBJECTIVE: The aim of our study was to determine whether ketamine's effect on acute postoperative pain could be enhanced and prolonged and analgesia consumption reduced if it was administered intramuscularly in repeated and escalating subanesthetic doses many hours before surgery. METHODS: Patients who were scheduled for tumor resection under general anesthesia were randomly and blindly given preoperative IM ketamine (K) or normal saline (placebo [P]) following 1 of 3 consecutive protocols (2 groups/protocol, 20 patients/group): 1 dose (25-mg ketamine or 1-mL saline) at 4 hours preoperatively (K1 or P1); 2 doses (10- and 25-mg ketamine or 1-mL saline twice) at 11 and 4 hours (K2 or P2); or 3 doses (5-, 10-, and 25-mg ketamine or 1-mL saline thrice) at 17, 11, and 4 hours preoperatively (K3 or P3). No other preoperative medications were given. Postoperatively, all patients received morphine (1.5 mg/bolus) via an intravenous patient-controlled analgesia (PCA) device. RESULTS: A total of 120 patients took part in the study. Patients' ages ranged from 15 to 75 years; mean weight (76 [14] kg; range, 50-120), gender (69 men, 51 women), and race were equally distributed among the groups. There were no significant differences in intraoperative parameters among the groups. The patients' mean self-rated 48-hour pain scores on a numerical rating scale were lower in the K2 and K3 groups than in their corresponding placebo groups (K2: 1.67 [1.04] vs P2: 3.62 [1.93] [P = 0.0004]; K3: 2.22 [1.37] vs P3: 3.25 [1.76] [P = 0.046]). These groups also used ∼35% less morphine compared with the placebo groups (K2: 28.4 [20.4] mg, K3: 26.6 [16.0] mg vs P2: 42.4 [30.4] mg, P3: 40.9 [21.2] mg [P ≤ 0.02]). Intravenous PCA usage among K2 and K3 patients was ∼50% less than the usage among their placebo counterparts (P < 0.05). The 1-ketamine-injection patients' pain scores and analgesic consumption were similar to those of their placebo groups. The 25-mg-ketamine injections caused dizziness that lasted up to 2 minutes. CONCLUSIONS: Our 48-hour data suggest that 2 or 3 escalating subanesthetic doses of IM ketamine injected consecutively hours before surgery attenuated postoperative pain and reduced morphine consumption in these subjects.