Comparison of analgesic effectiveness between nefopam and propacetamol in living kidney donors following rectus sheath block after hand-assisted living donor nephrectomy: a prospective, randomized controlled trial.

BACKGROUND: Nefopam and propacetamol are the most commonly used analgesics in postoperative multimodal analgesic regimens. Distinct mechanisms are involved in each drug's anti-nociceptive effects. No studies have compared pain relief efficacy between the two drugs in patients undergoing transplantation surgery. Here, we investigated whether the administration of nefopam or propacetamol to healthy living kidney donors who underwent rectus sheath block (RSB) for parietal pain could reduce the subsequent opioid dose necessary to produce adequate analgesia. METHODS: This prospective, randomized controlled trial included 72 donors undergoing elective hand-assisted living donor nephrectomy into two groups: propacetamol (n = 36) and nefopam (n = 36). Intraoperative RSB was performed in all enrolled donors. The primary outcome was the total volume of intravenous opioid-based patient-controlled analgesia (PCA) used on postoperative day 1 (POD 1). Additionally, the Numeric Rating Scale scores for flank (visceral) and umbilicus (parietal) pain at rest and during coughing were compared, and the Korean adaptation of the Quality of Recovery-15 Questionnaire (QoR-15 K) was evaluated on POD 1. RESULTS: Both groups had similar preoperative and intraoperative characteristics. On POD 1, the total amount of PCA infusion was significantly lower in the nefopam group than in the propacetamol group (44.5 ± 19.3 mL vs. 70.2 ± 29.0 mL; p < 0.001). This group also reported lower pain scores at the flank and umbilical sites and required fewer rescue doses of fentanyl in the post-anesthesia care unit. However, pain scores and fentanyl consumption in the ward were comparable between groups. The QoR-15 K scores were similar between groups; there were substantial improvements in breathing, pain severity, and anxiety/depression levels in the nefopam group. The incidences of postoperative complications, including sweating and tachycardia, were similar between groups. CONCLUSION: Compared with propacetamol, nefopam provides a greater analgesic effect for visceral pain and enhances the effects of blocks that reduce the opioid requirement in living kidney donors with parietal pain managed by RSB. TRIAL REGISTRATION: The trial was registered prior to patient enrollment in the clinical trial database using the Clinical Research Information Service (registration no. KCT0007351 , Date of registration 03/06/2022).

Application of TSPO-Specific Positron Emission Tomography Radiotracer as an Early Indicator of Acute Liver Failure Induced by Propacetamol, a Prodrug of Paracetamol.

Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis currently requires blood collection 24-72 h after APAP ingestion, necessitating repeated tests and hospitalization. Here, we assessed earlier ALF diagnosis using positron emission tomography (PET) imaging of translocator proteins (TSPOs), which are involved in molecular transport, oxidative stress, apoptosis, and energy metabolism, with the radiotracer [18F]GE180. We intraperitoneally administered propacetamol hydrochloride to male C57BL/6 mice to induce ALF. We performed in vivo PET/CT imaging 3 h later using the TSPO-specific radiotracer [18F]GE180 and quantitatively analyzed the PET images by determining the averaged standardized uptake value (SUVav) in the liver parenchyma. We assessed liver TSPO expression levels via real-time polymerase chain reaction, Western blotting, and immunohistochemistry. [18F]GE180 PET imaging 3 h after propacetamol administration (1500 mg/kg) significantly increased liver SUVav compared to controls (p = 0.001). Analyses showed a 10-fold and 4-fold increase in TSPO gene and protein expression, respectively, in the liver, 3 h after propacetamol induction compared to controls. [18F]GE180 PET visualized and quantified propacetamol-induced ALF through TSPO overexpression. These findings highlight TSPO PET's potential as a non-invasive imaging biomarker for early-stage ALF.

Evaluation of the Regulatory Required Post-Authorization Safety Study for Propacetamol: Nested Case-Control and Case-Time-Control Studies.

PURPOSE: Following the withdrawal of propacetamol in Europe owing to safety issues, the regulatory authority of South Korea requested a post-marketing surveillance study to investigate its safety profile. MATERIALS AND METHODS: We conducted nested case-control and case-time-control (CTC) analyses of cases and controls identified for outcomes of interest, including anaphylaxis, thrombosis, and Stevens-Johnson syndrome (SJS), using the claims database of South Korea, 2010-2019. Risk-set sampling was used to match each case with up to 10 controls for age, sex, cohort entry date, and follow-up duration. Exposure to anaphylaxis, thrombosis, and SJS was assessed within 7, 90, and 30 days of the index date, respectively. We calculated odds ratios (OR) with 95% confidence intervals (CIs) using conditional logistic regression to assess the risk of outcomes associated with propacetamol. RESULTS: We identified cases of anaphylaxis (n=61), thrombosis (n=95), and SJS (n=1) and matched them to controls (173, 268, and 4, respectively). In the nested case-control analysis, the ORs for anaphylaxis and SJS were inestimable given the small number of propacetamol users during the risk period; meanwhile, the OR for thrombosis was 1.60 (95% CI 0.71-3.62). In the CTC design, the effect estimate was only estimated for thrombosis (OR 0.56, 95% CI 0.09-3.47). CONCLUSION: In both nested case-control and CTC analyses, propacetamol was not associated with an increased risk of anaphylaxis, thrombosis, or SJS. The findings from this study, which used routinely collected clinical data, provide reassuring real-world evidence regarding the safety of propacetamol in a nationwide population to support regulatory decision-making.

Propacetamol in dogs: First description of its pharmacokinetics after intravenous and oral administration.

Propacetamol is a prodrug form of paracetamol (APAP) licensed for human use as a pain reliever in postoperative care. It is prescribed if APAP cannot be administered orally or rectally to a patient and for patients in whom nonsteroidal anti-inflammatory drugs are contraindicated. In this study, we aimed to quantify the pharmacokinetics of APAP and its metabolites, paracetamol sulfate (PS), paracetamol glucuronide (PG), and N-acetyl-p-benzoquinone imine (NAPQI), after a single oral and intravenous (IV) administration of 30 mg/kg of propacetamol to six healthy adult Labrador dogs according to a 2 × 2 crossover study. The analyses were performed using a validated HPLC-MS/MS method. PS and PG exposures were higher than that of APAP, while NAPQI concentrations were constantly below the detection limit of the analytical method. IV propacetamol administration produced 30% more APAP than oral administration. However, propacetamol released a significantly lower amount of active moiety in dogs than in humans. The propacetamol dose administered in this study did not produce plasma APAP concentrations above the threshold sufficient to provide analgesia in adult humans (4 µg/mL). In conclusion, direct IV injection of APAP instead of propacetamol might be a better clinical option for pain relief in dogs.

A narrative review of paracetamol-induced hypotension: Keeping the patient safe.

AIM: To understand the prevalence and epidemiology of paracetamol-induced hypotension and clinical implications for contemporaneous practice. DESIGN: Narrative review. METHODS: In May and June 2020, an open-date literature search of English publications indexed in ProQuest, PubMed, and EBSCO was conducted with the search terms 'acetaminophen' and 'hypotension' and related search combinations ('paracetamol', 'propacetamol', 'low blood pressure', 'fever', 'sepsis', and 'shock') to identify peer-reviewed publications of blood pressure changes after paracetamol administration in humans. RESULTS: A pattern of blood pressure reduction following the administration of paracetamol is demonstrated in the 27 studies included in this review. Haemodynamic intervention often followed persistent blood pressure reduction, and was greatest in febrile critically ill patients who received parenteral paracetamol.

Risk Factors for Intravenous Propacetamol-Induced Blood Pressure Drop in the Neurointensive Care Unit: A Retrospective Observational Study.

BACKGROUND: Intravenous propacetamol is commonly used to control fever and pain in neurocritically ill patients in whom oral administration is often difficult. However, several studies reported that intravenous propacetamol may cause blood pressure drop. Thus, we aimed to investigate the occurrence and risk factors for intravenous propacetamol-induced blood pressure drop in neurocritically ill patients. METHODS: This retrospective study included consecutive patients who were administered intravenous propacetamol in a neurointensive care unit at a single tertiary academic hospital between April 2013 and June 2020. The exact timing of intravenous propacetamol administration was collected from a database of the electronic barcode medication administration system. Blood pressure drop was defined as a systolic blood pressure below 90 mm Hg or a decrease by 30 mm Hg or more. Blood pressure, pulse rate, and body temperature were collected at baseline and within 2 h after intravenous propacetamol administration. The incidence of blood pressure drop was evaluated, and multivariable logistic regression analysis was performed to identify risk factors for blood pressure drop events. RESULTS: A total of 16,586 instances of intravenous propacetamol administration in 4916 patients were eligible for this study. Intravenous propacetamol resulted in a significant decrease in systolic blood pressure (baseline 131.1 ± 17.8 mm Hg; within 1 h 124.6 ± 17.3 mm Hg; between 1 and 2 h 123.4 ± 17.4 mm Hg; P < 0.01). The incidence of blood pressure drop events was 13.5% within 2 h after intravenous propacetamol. Older age, lower or higher baseline systolic blood pressure, fever, higher Acute Physiology and Chronic Health Evaluation II score, and concomitant administration of vasopressors/inotropes or analgesics/sedatives were significant factors associated with the occurrence of blood pressure drop events after intravenous propacetamol administration. CONCLUSIONS: Intravenous propacetamol can induce hemodynamic changes and blood pressure drop events in neurocritically ill patients. This study identified the risk factors for blood pressure drop events. On the basis of our results, judicious use of intravenous propacetamol is warranted for neurocritically ill patients with risk factors that make them more susceptible to hemodynamic changes.

The antipyretic efficacy and safety of propacetamol compared with dexibuprofen in febrile children: a multicenter, randomized, double-blind, comparative, phase 3 clinical trial.

BACKGROUND: We aimed to compare the antipyretic efficacy, safety, and tolerability between oral dexibuprofen and intravenous propacetamol in children with upper respiratory tract infection (URTI) presenting with fever. METHODS: Patients aging from 6 months to 14 years admitted for URTI with axillary body temperature ≥ 38.0 °C were enrolled and randomized into the study or control group. Patients in the study group were intravenously infused with propacetamol and subsequently oral placebo medication was administered. Patients in the control group were intravenously infused with 100 mL of 0.9% sodium chloride solution without propacetamol and then oral dexibuprofen was administered. We checked the body temperature of all patients at 0.5 h (hr), 1 h, 1.5 h, 2 h, 3 h, 4 h, and 6 h after oral placebo or dexibuprofen had been applied. RESULTS: A total of 263 patients (125 in the study group) were finally enrolled. The body temperatures of patients in the study group were significantly lower until 2 h after administration (37.73 ± 0.58 vs 38.36 ± 0.69 °C (p < 0.001), 37.37 ± 0.53 vs 37.88 ± 0.69 °C (p < 0.001), 37.27 ± 0.60 vs 37.62 ± 0.66 °C (p < 0.001), 37.25 ± 0.62 vs 37.40 ± 0.60 °C (p = 0.0452), at 0.5 h, 1 h, 1.5 h, and 2 h, respectively). The two groups showed no significant differences in terms of the range of body temperature decrease, the Area Under the Curve of body temperature change for antipyretic administration-and-time relationship, the maximum value of body temperature decrease during the 6 h test period, the number of patients whose body temperature normalized (< 37.0 °C), the mean time when first normalization of body temperature, and the development of adverse events including gastrointestinal problem, elevated liver enzyme, and thrombocytopenia. CONCLUSIONS: Intravenous propacetamol may be a safe and effective choice for pediatric URTI patients presenting with fever who are not able to take oral medications or need faster fever control. TRIAL REGISTRATION: CRIS KCT0002888 . Date of registration: July 31st, 2013.

Hemodynamic changes in patients with influenza A after propacetamol infusion in the emergency department.

OBJECTIVES: Recently, there has been an emerging clinical data suggesting that intravenous propacetamol may cause iatrogenic hypotension. The primary objective of this study was to evaluate hemodynamic changes after propacetamol infusion in the emergency department (ED) with the patients of influenza A. Secondary objective was to assess the incidence of propacetamol-induced significant hypotension and to evaluate factors associated with this adverse effect by comparing two groups of patients with or without a significant reduction in blood pressure (BP). METHODS: We retrospectively reviewed the medical records of the patients with laboratory-confirmed influenza A who received intravenous propacetamol for the control of fever in the ED during the 2015-16 influenza season. RESULTS: 101 patients of influenza A were included in this study. Overall, all the vital signs including BP, pulse rate and body temperature recorded after propacetamol administration were lower than the pre-infusion values. A significant reduction in BP was observed in 30 (29.7%) patients and 6 (20%) of them required crystalloid infusion. Interestingly, pre-infusion BPs were higher in the group of propacetamol-induced significant hypotension, yet there was no difference in post-infusion BPs between the groups. DISCUSSION: To our knowledge this is the first study on the effect of intravenous propacetamol in the ED patients with influenza A infection. We hypothesized that the group with a significant reduction in BP could have higher sympathetic tone, consequently showing higher pre-infusion BPs and pulse rate. And there was no difference in post-infusion BPs because baroreflex homeostasis could compensate further decrease in BPs.

Hemodynamic changes after propacetamol administration in patients with febrile UTI in the ED.

OBJECTIVES: Clinical studies have indicated that transient hypotension can occur after propacetamol administration. This study aimed to analyze the hemodynamic changes after propacetamol administration in patients visiting the ED due to febrile UTI. We also examined the incidence of propacetamol-induced hypotension and compared the clinical characteristics of patients with persistent hypotension, defined as requiring additional fluids or vasopressors, to those with transient hypotension. METHODS: A retrospective analysis of the electronic medical records of patients who visited the ED between June 2015 and May 2016, were diagnosed with febrile UTI, and treated with propacetamol, was conducted. RESULTS: We included 195 patients in this study; of these, 87 (44.6%) showed hypotension. In all patients, significant decreases in systolic blood pressure (SBP; 135.06±20.45mmHg vs 117.70±16.41mmHg), diastolic blood pressure (DBP; 79.74±12.17mmHg vs 69.69±10.96mmHg), and heart rate (97.46±17.14mmHg vs 90.72±14.90mmHg) were observed after propacetamol administration. The basal SBP and DBP were higher in the hypotension than in the non-hypotension group (basal SBP: 144.4±22.3mmHg vs 127.6±15.3mmHg; basal DBP: 83.3±12.6mmHg vs 76.9±11.0mmHg). Patients with persistent hypotension had a lower baseline BP, which was not elevated despite fever, and a higher rate of bacteremia than those with transient hypotension. CONCLUSIONS: Although febrile UTI patients treated with propacetamol in the ED showed hemodynamic changes, these changes did not have a large effect on their prognosis. However, in patients who showed bacteremia or a normal initial BP despite fever, the possibility of developing persistent hypotension should be considered.

Comparison of Propacetamol plus Fentanyl and Fentanyl alone with Patient Controlled Analgesia after Total Knee Arthroplasty

OBJECTIVE: Opioid analgesics, for postoperative pain management, are an indispensable group of medication; however, they also have a variety of adverse drug reactions (ADR). Multimodal methods, combining non-opioid analgesics with opioid analgesics, have been investigated to increase the effects of analgesics and reduce ADR with opioid-sparing effects. The purpose of this study was to compare the effects of patient-controlled analgesia (PCA) with fentanyl alone, and PCA with fentanyl and intravenous (i.v.) propacetamol to determine the effects of pain control, cumulative opioid usage, and opioid ADR. METHODS: The subjects were patients who underwent total knee arthroplasty at the Seoul Veterans hospital from January 1, 2015 to December 31, 2016. The study period was from postoperative day 0 (POD0) to day 3 (POD3), and the retrospective study was conducted using electronic medical records. RESULTS: Pain severity was significantly low at POD1 (p = 0.017), POD2 (p = 0.003), and POD3 (p = 0.002) in the multimodal group. The fentanyl only group frequently reported both moderate and severe pain at a statistically significant level. This was consistent with the analysis of the pro re nata (PRN) intramuscular analgesia usage at the time of numerical rating scale (NRS) 4 and above. The opioid-sparing effect confirmed that the average opioid dose equivalent to i.v. morphine dose was 9.4 mg more than that used for the multimodal group in the fentanyl only group. The ADRs and length of stay between the two groups were not statistically different. CONCLUSION: The results of this study suggest that the combination therapy of fentanyl and i.v. propacetamol is superior to fentanyl monotherapy.

Intravenous Paracetamol Dosing Guidelines for Pain Management in (pre)term Neonates Using the Paediatric Study Decision Tree.

BACKGROUND: Intravenous paracetamol (acetaminophen) has not been licensed for analgesia in preterm neonates or infants < 2 years, respectively, in Europe and the United States. A variety of dosing regimens is therefore used off-label. Because evidence supports the use of the same target mean steady state paracetamol concentration (Cssmean, 9-11 mg/L) for pain relief in neonates compared to older children and adults, dosing regimens based on this Cssmean were evaluated in a two-step approach. METHODS: First, a systematic search was performed to provide pharmacokinetic (PK)-based dosing guidelines for pain in neonates (with subsequent searches on safety in these papers). Second, concentration-time profiles based on these dosing guidelines were generated to provide a dosing advice for paracetamol to treat neonatal pain. RESULTS: Of 2334 potentially relevant articles, 9 studies were included. For typical term neonates, dosages specified in packaging (labels) resulted in Cssmean below target (7.65 mg/L), while dosages from investigator-initiated studies resulted in either a Cssmean above (15.31), or around the target (11.78 and 10.21) for (pre)term neonates >32 weeks. Only one study suggested a dosing resulting in a tailored concentration (8.7) in preterm neonates <32 weeks. CONCLUSION: A loading dose 20 mg/kg, followed by 10 mg/kg/6h is recommended for 32-44 weeks' neonates, which is supported by short-term safety. For neonates < 32 weeks, a loading dose of 12 mg/kg and a maintenance dose of 6mg/kg/6h seems to lead to the target Cssmean, though additional clinical studies are needed to support its safety.

Single dose intravenous paracetamol or intravenous propacetamol for postoperative pain.

statement The mission of the Cochrane Nursing Care Field (CNCF) is to improve health outcomes through increasing the use of the Cochrane Library and supporting Cochrane's role by providing an evidence base for nurses and healthcare professionals who deliver, lead or research nursing care. The CNCF produces Cochrane Corner columns, summaries of recent nursing-care-relevant Cochrane Reviews that are regularly published in collaborating nursing-related journals. Information on the processes CNCF has developed can be accessed at: cncf.cochrane.org/evidence-transfer-program-review-summaries . This is a Cochrane review summary of: McNicol ED, Ferguson MC, Haroutounian S et al (2016) Single dose intravenous propacetamol or intravenous paracetamol for postoperative pain. Cochrane Database of Systematic Reviews. Issue 10. CD007126. doi: 10.1002/14651858.CD007126.pub3.

Successful Use of [14C]Paracetamol Microdosing to Elucidate Developmental Changes in Drug Metabolism.

BACKGROUND: We previously showed the practical and ethical feasibility of using [14C]-microdosing for pharmacokinetic studies in children. We now aimed to show that this approach can be used to elucidate developmental changes in drug metabolism, more specifically, glucuronidation and sulfation, using [14C]paracetamol (AAP). METHODS: Infants admitted to the intensive care unit received a single oral [14C]AAP microdose while receiving intravenous therapeutic AAP every 6 h. [14C]AAP pharmacokinetic parameters were estimated. [14C]AAP and metabolites were measured with accelerator mass spectrometry. The plasma area under the concentration-time curve from time zero to infinity and urinary recovery ratios were related to age as surrogate markers of metabolism. RESULTS: Fifty children [median age 6 months (range 3 days-6.9 years)] received a microdose (3.3 [2.0-3.5] ng/kg; 64 [41-71] Bq/kg). Plasma [14C]AAP apparent total clearance was 0.4 (0.1-2.6) L/h/kg, apparent volume of distribution was 1.7 (0.9-8.2) L/kg, and the half-life was 2.8 (1-7) h. With increasing age, plasma and urinary AAP-glu/AAP and AAP-glu/AAP-sul ratios significantly increased by four fold, while the AAP-sul/AAP ratio significantly decreased. CONCLUSION: Using [14C]labeled microdosing, the effect of age on orally administered AAP metabolism was successfully elucidated in both plasma and urine. With minimal burden and risk, microdosing is attractive to study developmental changes in drug disposition in children.

Propacetamol poses a potential harm of adverse hypotension in male and older patients.

PURPOSE: Researchers recently suggested intravenous paracetamol as a potential cause of hypotension. We aimed to investigate risk factors of paracetamol- and propacetamol-associated adverse drug reactions (ADRs) in Korean individuals. METHODS: All adverse hypotension cases, regardless of suspected drug, and all ADRs associated with paracetamol and propacetamol use were collected from the Korea Adverse Event Reporting System database between 2011 and 2014. The seriousness, causality, and type of ADR were classified. RESULTS: Of 4,771 cases of adverse hypotension, 403 (8.4%) were reported to be related to propacetamol. This was comparable to the rate of hypotension associated with fentanyl (454, 9.5%), the major suspected drug of hypotension. Paracetamol-associated hypotension accounted for merely 1.2% (55 cases) of all hypotension cases. Among ADRs associated with propacetamol use, hypotension was the most common (37.1%), whereas cutaneous reactions were the primary paracetamol-associated ADR. Propacetamol/paracetamol-associated hypotension was frequently recorded in older patients (≥54 years) (53.9 ± 25.8 vs. 42.8 ± 21.7, P < 0.001) and taking more concomitant drugs (1.9 ± 5.0 vs. 1.1 ± 3.2, P < 0.001). Also, compared with other ADRs associated by propacetamol/paracetamol, hypotension was more commonly assessed as a serious outcome (27.3% vs. 11.4%, P < 0.001). Regarding concomitant medications, the risk for hypotension associated with propacetamol was significantly increased in patients simultaneously taking antibacterials (J01), cold preparations (R05), drugs for acid related disorders (A02), blood substitutes (B05), or antithrombotics (B01). CONCLUSIONS: Propacetamol was found to be a major suspected drug of pharmacologically associated hypotension in Korea. Older and male patients taking medications in combination with propacetamol/paracetamol should undergo monitoring of their blood pressure. Copyright © 2017 John Wiley & Sons, Ltd.

Clinically significant hemodynamic alterations after propacetamol injection in the emergency department: prevalence and risk factors.

Propacetamol, a water-soluble prodrug form of paracetamol, is hydrolyzed by esterase to generate paracetamol in the blood. Each gram of propacetamol is equal to 0.5 g of paracetamol. It has been reported to cause hypotension in critically ill patients with a fever. We aimed to investigate the hemodynamic effects of propacetamol for the control of fever in patients with diverse severities of illness who were managed in the emergency department (ED). We also aimed to identify clinical factors related to significant hemodynamic alterations in ED patients. This was a retrospective study of 1507 ED patients who received propacetamol. Significant hemodynamic alterations were defined as systolic blood pressure (SBP) <90 mmHg or diastolic blood pressure (DBP) <60 mmHg, or a drop in SBP >30 mmHg, which required treatments with a bolus of fluid or vasopressor administration. Postinfusion SBP and DBP were significantly lower than the preinfusion SBP and DBP. A clinically significant drop in BP occurred in 162 (10.7 %) patients, and interventions were necessary. Among the predictors assessed, congestive heart failure (OR 6.21, 95 % CI 2.67-14.45) and chills (OR 3.10, 95 % CI 2.04-4.70) were independent factors for a significant hemodynamic change. Administration of propacetamol can provoke a reduction in BP in ED patients. This reduction was clinically significant for 10 % of infusions. Clinicians should be aware of this potential deleterious effect, especially in patients with congestive heart failure or who experience chills prior to the administration of propacetamol.

Propacetamol as an alternative of ketorolac for postoperative pain management using patient-controlled analgesia

BACKGROUND: The objective of this study was to examine effect of propacetamol in comparison with ketorolac in intravenous patient-controlled analgesia after gynecologic surgeries. METHODS: Patients aged 18 to 70 years and undergoing laparoscopic gynecologic surgeries were selected. They were randomly allocated to either group K (180 mg of ketorolac with fentanyl and ramosetron) or group P (10 g of propacetamol with fentanyl and ramosetron). Their vital signs and visual analogue scale (VAS) were examined six times (0 min, 15 min, 30 min, 60 min, 12 h, and 24 h) and laboratory workup was done 48 hours after PCA application. Development of side effects was examined 15 minutes after the PCA application. Data from 111 patients were used for the final analysis. RESULTS: There were no significant differences in changes of systolic and diastolic blood pressures, heart rate, body temperature, and VAS between the groups (P = 0.325, 0.835, 0.346, 0.524, and 0.382, respectively). There were significant differences in the levels of hemoglobin, hematocrit, blood urea nitrogen, and international normalized ratio but it was not clinically meaningful. The development of vomiting, dizziness, and headache were not significantly different between the groups and no patient developed pruritus. Although the overall number of patients with nausea was higher in group P with statistical significance (P = 0.002), there were no significant differences between the groups when examined at each detection time. CONCLUSIONS: The present study suggested propacetamol as a possible alternative of ketorolac in postoperative care after laparoscopic gynecologic surgeries.

Propacetamol as an alternative of ketorolac for postoperative pain management using patient-controlled analgesia

BACKGROUND: The objective of this study was to examine effect of propacetamol in comparison with ketorolac in intravenous patient-controlled analgesia after gynecologic surgeries. METHODS: Patients aged 18 to 70 years and undergoing laparoscopic gynecologic surgeries were selected. They were randomly allocated to either group K (180 mg of ketorolac with fentanyl and ramosetron) or group P (10 g of propacetamol with fentanyl and ramosetron). Their vital signs and visual analogue scale (VAS) were examined six times (0 min, 15 min, 30 min, 60 min, 12 h, and 24 h) and laboratory workup was done 48 hours after PCA application. Development of side effects was examined 15 minutes after the PCA application. Data from 111 patients were used for the final analysis. RESULTS: There were no significant differences in changes of systolic and diastolic blood pressures, heart rate, body temperature, and VAS between the groups (P = 0.325, 0.835, 0.346, 0.524, and 0.382, respectively). There were significant differences in the levels of hemoglobin, hematocrit, blood urea nitrogen, and international normalized ratio but it was not clinically meaningful. The development of vomiting, dizziness, and headache were not significantly different between the groups and no patient developed pruritus. Although the overall number of patients with nausea was higher in group P with statistical significance (P = 0.002), there were no significant differences between the groups when examined at each detection time. CONCLUSIONS: The present study suggested propacetamol as a possible alternative of ketorolac in postoperative care after laparoscopic gynecologic surgeries.

Predictive Factor of Blood Pressure Lowering in Patients with Fever Using Propacetamol

PURPOSE: This study aimed to identify predictive factors for decreased blood pressure in patients prescribed with propacetamol in the emergency room using clinical and laboratory indicators of sepsis. METHODS: Among patients aged 18 years or older with a fever, who visited Chungbuk National University hospital's emergency room between July and December of 2014, 246 patients underwent intravenous infusion of propacetamol to control body temperature. Of these, 112 patients fulfilled all study requirements. Patients whose systolic or diastolic blood pressure dropped below 90 mmHg or 60 mmHg, respectively, were included in the blood pressure decline group. Additional inclusion criteria were a decline in systolic blood pressure of more than 30-mmHg and thereby treated with fluids or inotropics after intravenous infusion of propacetamol. Remaining patients were included in the blood pressure maintenance group. The relationship of each factor between the two groups was then investigated. RESULTS: Twenty-nine patients (25.9%) showed a significant decrease in blood pressure, and among many factors, high-sensitivity C-reactive protein (hs-CRP) (cut off value, 11.86; sensitivity, 72.4%; specificity, 69.9%; area under curve [AUC], 0.698) and procalcitonin (cut off value, 0.67; sensitivity, 75.9%; specificity, 60.2%; AUC, 0.667) levels showed a statistically significant effect. Of the 29 patients with a decrease in blood pressure, 10 patients received fluids and inotropics; procalcitonin in particular showed a significant effect. CONCLUSION: When propacetamol is administered to patients at the emergency room, and if hs-CRP or procalcitonin levels are high, there is an increased risk of a decrease in blood pressure. In particular, if procalcitonin levels are high, aggressive treatment is required, such as administration of inotropics in addition to fluids.

Galangin Prevents Acute Hepatorenal Toxicity in Novel Propacetamol-Induced Acetaminophen-Overdosed Mice.

Acetaminophen (APAP) overdose causes severe liver and kidney damage. APAP-induced liver injury (AILI) represents the most frequent cause of drug-induced liver failure. APAP is relatively insoluble and can only be taken orally; however, its prodrug, propacetamol, is water soluble and usually injected directly. In this study, we examined the time-dependent effects of AILI after propacetamol injection in mice. After analyses of alanine aminotransferase and aspartate aminotransferase activities and liver histopathology, we demonstrated that a novel AILI mouse model can be established by single propacetamol injection. Furthermore, we compared the protective and therapeutic effects of galangin with a known liver protective extract, silymarin, and the only clinical agent for treating APAP toxicity, N-acetylcysteine (NAC), at the same dose in the model mice. We observed that galangin and silymarin were more effective than NAC for protecting against AILI. However, only NAC greatly improved both the survival time and rate consequent to a lethal dose of propacetamol. To decipher the hepatic protective mechanism(s) of galangin, galangin pretreatment significantly decreased the hepatic oxidative stress, increased hepatic glutathione level, and decreased hepatic microsomal CYP2E1 levels induced by propacetamol injection. In addition, propacetamol injection also reproduced the probability of APAP-induced kidney injury (AIKI), appearing similar to a clinical APAP overdose. Only galangin pretreatment showed the protective effect of AIKI. Thus, we have established a novel mouse model for AILI and AIKI using a single propacetamol injection. We also demonstrated that galangin provides significant protection against AILI and AIKI in this mouse model.

A Comparative Efficacy of Propacetamol and Ketorolac in Postoperative Patient Controlled Analgesia.

BACKGROUND: Ketorolac has been used as a postoperative analgesia in combination with opioids. However, the use of ketorolac may produce serious side effects in vulnerable patients. Propacetamol is known to induce fewer side effects than ketorolac because it mainly affects the central nervous system. We compared the analgesic effects and patient satisfaction levels of each drug when combined with fentanyl patient-controlled analgesia (PCA). METHODS: The patients were divided into two groups, each with n = 46. The patients in each group were given 60 mg of ketorolac or 2 g of propacetamol (mixed with fentanyl) for 10 minutes. The patients were then given 180 mg of ketorolac or 8 g of propacetamol (mixed with fentanyl and ramosetron) through PCA. We assessed the visual analogue pain scale (VAS) at the time point immediately before administration (baseline) and at 15, 30, and 60 minutes, and 24 hours after administration. Also, the side effects of each regimen and each patient's degree of satisfaction were assessed. RESULTS: There was a significant decline in the VAS score in both groups (P < 0.05). However, there were no significant differences in the VAS scores between the groups at each time point. Satisfaction scores between the groups showed no significant difference. CONCLUSIONS: The efficacy of propacetamol is comparable to that of ketorolac in postoperative PCA with fentanyl.