Acetaminophen Infusion Research Articles

Outcomes of acetaminophen infusion on visual analogue scale with varying pain intensity during labour, A randomized controlled trial

Objective: Acetaminophen (Paracetamol) is the most widely used analgesic. We aimed to determine its efficacy in labour with varying pain intensity, to make labour less painful for women. Methods: This randomized controlled trial was conducted on primigravida’s in their active phase of first stage of labour at Pharmacology department of Army Medical College, National University of Medical Sciences in collaboration with Gynecology department of Pak Emirates Military hospital, Rawalpindi. It was a registered trial with trial number of IRCT20220308054220N1. Duration of study was from May 2022 to October 2022. Patients were divided into two groups, Group-I received two doses of I/V 100 ml normal saline whereas Group-II received I/V two doses of 1000 mg acetaminophen in 100 ml normal saline. Calculated sample size was 130, 65 in each group. Visual analogue scale was used as a tool for data measurement. Data was analysed using split plot anova test. Results: Mean VAS in acetaminophen infusion group was found to be less than placebo for 1st dose, but this effect was apparent only one hour after 2nd dose intervention. The difference in means between groups was statistically significant only for 1st dose with p-value of 0.003 (for second dose p-value 0.21). In acetaminophen infusion group, for both doses mean VAS decreased as an immediate effect of drug, but then it increased with time. The difference in VAS between intervals had p-value of <0.001 for 1st dose and 0.005 for 2nd dose. Conclusion: Acetaminophen is an effective non opioid labour analgesic in active phase of first stage of labour. doi: https://doi.org/10.12669/pjms.40.10.8425 How to cite this: Najeeb W, Komal N, Noor M, Khan MA, Chaudry A. Outcomes of acetaminophen infusion on visual analogue scale with varying pain intensity during labour, A randomized controlled trial. Pak J Med Sci. 2024;40(10):2163-2169. doi: https://doi.org/10.12669/pjms.40.10.8425 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Efficacy of intravenous acetaminophen on postoperative shivering: A meta-analysis of randomized controlled trials.

Postoperative shivering (POS) is a common and vital complication after anesthesia, which may result in serious consequences and uncomfortable experiences. Acetaminophen has been used to treat fever and mild to moderate pain. However, there is not enough evidence to prove its advantage for POS. This meta-analysis aimed to explore the prophylactic use of acetaminophen as a valid agent for POS. Two researchers independently searched PubMed, the Cochrane Library, and Embase for controlled clinical trials. The meta-analysis of randomized controlled trials (RCTs) was performed by Review Manager. Nine trials with 856 patients were included in our meta-analysis. Acetaminophen significantly reduced POS compared with placebo (pooled risk ratio [RR]: 0.43, 95% confidence interval [CI]: 0.35-0.52). What is more, not only 15 mg/kg but also 1000 mg intravenous acetaminophen could reduce the incidence of shivering compared with placebo. Our present meta-analysis demonstrates that the intravenous prophylactic infusion of acetaminophen may prevent POS, and the results may provide new evidence to expand the clinical value of acetaminophen in addition to its routine usage.

Effect of infusion time of intravenous acetaminophen on blood pressure in the intensive care unit.

To understand the effect of prolonged intravenous acetaminophen infusion on blood pressure. We retrospectively studied a cohort of intensive care patients receiving initial intravenous acetaminophen. We used propensity score matching to adjust for differences between patients who were classified into two groups: control (acetaminophen infusion for 15 minutes) and prolonged administration (acetaminophen infusion for > 15 minutes). After acetaminophen administration, diastolic blood pressure was unchanged in the control group, and was significantly lower at 30 and 60 minutes in the prolonged administration group. Prolonged duration of acetaminophen infusion did not prevent acetaminophen-induced blood pressure reduction.

Perioperative Intravenous Lidocaine Infusion for Postlaparoscopic Cholecystectomy Pain.

To compare intravenous lidocaine infusion adjunct to NSAID and Acetaminophen with regular analgesics for postoperative mean pain score and mean ambulation time after laparoscopic cholecystectomy. Randomised controlled trial. Department of General Surgery, Islamabad Medical Complex, (IMC), from March 2020 to December 2021. Sixty (n=60) adult patients, both males and females between the ages of 18-60 years planned for laparoscopic cholecystectomy, were selected and randomly allocated to two groups of treatment (Lidocaine and Ringer Lactate). The control group did not receive any other placebo other than Ringer Lactate infusion. Both groups received Intramuscular Diclofenac 12 hourly and intravenous acetaminophen infusion 8 hourly. Postoperative pain 2, 6, 12 and 24 hours (h) and mean ambulation time were compared in both groups. Mean VAS (Visual Analogue Scale) of group 1 versus group 2 at 2 h, 6 h, 12 h and 24 h were 3.47 ± 0.82 vs. 6.27 ± 0.52 (p=<0.001), 2.7 ± 0.75 vs. 4.8 ± 0.8 (p<0.001), 2.0 ± 0.49 vs. 3.93 ± 0.94 (p<0.001), 0.73 ± 0.82 vs. 2.2 ± 0.61 (p<0.001). Time for spontaneous ambulation after surgery was 5.57 ± 1.55 hours for Group 1 versus 7.3 ± 1.9 hours for Group 2 (p<0.001). Pain scores at all-time intervals were lower, and ambulation time was shorter in patients who received intravenous infusion of lidocaine as compared to patients who received only regular analgesics for laparoscopic cholecystectomy. Ambulation time, Laparoscopic cholecystectomy, Postoperative pain.

Evaluation of efficacy and safety of subcutaneous acetaminophen in geriatrics and palliative care (APAPSUBQ)

IntroductionSubcutaneous infusion (SC) or hypodermoclysis is an old perfusion technique that is often used off-label although it has been shown to be effective. Acetaminophen (paracetamol) subcutaneous injection is performed in some centers despite the lack of conclusive evidence on its effectiveness. This study aims to evaluate the efficacy of subcutaneous infusion of Acetaminophen in the treatment of pain and fever in geriatrics and in palliative care and to determine its safety profile and possible side effects.Material and methodsThis experimental study was conducted between 2018 and 2019 on adult patients in palliative care or in geriatrics in several hospitals and nursing homes in Lebanon. Primary outcomes were change in temperature; change in pain score on the numerical rating scale (NS) or on the Algoplus scale after 60 min from the start of the infusion; and the appearance of local side effects at the infusion site. Changes in the various parameters at 30 min and 180 min were also evaluated as secondary outcomes.ResultsThirty-one patients were included in the study, with a total of 120 doses of acetaminophen. At 60 min, the mean decrease in pain on the NS was 5.35 points, while the mean decrease in temperature was 0.79 degrees Celsius. At 60 min, 75%, CI = [47.62-92.73] of the patients who received acetaminophen for pain and 66.67%, CI = [38.38-88.17] of those who received it for fever had clinically significant improvement. The overall effect of subcutaneous acetaminophen, defined as any clinically significant effect on pain or fever, was 70.97%, CI = [51.96-85.78]. The overall effect at 30 min and at 180 min was 23.33%, CI = [9.93-42.28] and 87.10%, CI = [70.17-96.37], respectively. The side effects reported 30 min after the injection and observed after at least one of the doses were: local edema in 16 patients (51.61%), induration in one patient (3.23%), local pain in one patient (3.23%) and local heat in one patient (3.23%). At 180 min, only 2 patients (6.45%) still had edema at the infusion site.ConclusionSubcutaneous administration of acetaminophen is effective and well tolerated in geriatric and palliative care patients. It is appropriate when no other route is available, especially for home-based care. Comparative studies are needed to allow the expansion of this practice.

Comparison between the Effects of Acetaminophen, Dexmedetomidine, and Normal Saline Infusion on Pain Severity after Cataract Surgery.

Cataract surgery is one of the most common eye surgeries, which is currently performed under topical anesthesia using sedative medications. Dexmedetomidine and acetaminophen are good candidates for analgesia in other circumstances, however, this study aimed to evaluate the effect of dexmedetomidine or acetaminophen infusion and normal saline (NS) alone compared with the control group on the severity of pain in cataract surgery. In this parallel randomized controlled clinical trial, the effect of dexmedetomidine or acetaminophen infusion and NS on level of pain, vital signs, recovery status, and surgeon satisfaction during cataract surgery were assessed. One hundred and thirty-five patients between the age of 50-80 years undergoing cataract surgery were recruited on a consecutive basis and randomized into three groups receiving acetaminophen (15 mg/kg), dexmedetomidine (0.5 μgr/kg), and NS. Baseline vital signs, blood pressure, arterial oxygen saturation, respiratory and heart rate at certain time-points including the start of surgery, 5, 10, and 15 min after surgery, after arrival to the recovery room, 20, 40, 60 min after recovery were measured. Pain intensity and drugs side effects were also recorded after surgery. Level of respiratory depression was higher in patients receiving dexmedetomidine. Heart rate and oxygen saturation percentage had no significant differences in the three groups as well as pain intensity. Acetaminophen was as effective as dexmedetomidine with lower side effects and higher surgeons' satisfaction, without any interference with cardiovascular and respiratory parameters. Acetaminophen infusion should be considered as an acceptable analgesic drug for cataract surgery.

Postoperative around-the-clock administration of intravenous acetaminophen for pain control following robot-assisted radical prostatectomy

The objective of this study was to examine the impact of around-the-clock (ATC) administration of intravenous (IV) acetaminophen following robot-assisted radical prostatectomy (RARP). Intravenous infusion of acetaminophen was started on the day of the operation at 1000 mg/dose every 6 h, and the infusion was continued on a fixed schedule until postoperative day 2 a.m. In a retrospective observational study, we compared 127 patients who were administered IV acetaminophen on a fixed schedule (ATC group) with 485 patients who were administered analgesic drugs only as needed (PRN group). We investigated postoperative pain intensity and additional analgesic consumption on postoperative day 0, 1, 2, 3, and 5 between the two groups. Postoperative pain scores were significantly lower in the ATC group than in the PRN group at 1 and 2 days, and this period matched the duration of ATC administration of IV acetaminophen. Postoperative frequency of rescue analgesia was significantly lower in the ATC group than in the PRN group at postoperative 0, 1, and 2 days. ATC administration of IV acetaminophen has the potential to be a very versatile and valuable additional dose to achieve appropriate postoperative analgesia in patients with RARP.

Comparison of acetaminophen and nalbuphine in attenuating hemodynamic response to tracheal intubation.

Laryngoscopy and tracheal intubation causes sympathetic over activity in the form of increased heart rate and blood pressure, which may lead to deleterious effects. Opioid drugs like fentanyl and nalbuphine are routinely used to attenuate this response during intubation. A few studies have claimed that acetaminophen is efficacious for this purpose too. Various studies have explored its role in blunting of pressor response but none have compared it with nalbuphine. We compared these drugs with the purpose, if both drugs are equally effective; acetaminophen would be a better alternative to nalbuphine without adverse effects of an opioid. Objectives: The objective of this study was to compare the efficacy of acetaminophen and nalbuphine in attenuating hemodynamic response during tracheal intubation. Study Design: Randomized, double-blind clinical trial. Setting: Main operation theatre complex of Fauji Foundation Hospital Rawalpindi. Period: From August to December 2018. Material &amp; Methods: After obtaining permission from institutional ethical review committee of Fauji Foundation Hospital Rawalpindi. 60 Patients of ASA physical status I and II, aged 30 to 55 years, undergoing abdominal surgical procedure of 1 to 3 hour duration were randomly divided into two groups. Patients in group N received nalbuphine hydrochloride 0.15 mg/kg body weight intravenously, 30 minutes before induction. Patients in group P received acetaminophen infusion (paracetamol) 15mg/kg body weight intravenously, 30 minutes before induction. Systolic and diastolic blood pressures were measured manually and heart rate by pulse oximeter. Observations were made before giving analgesics, during induction, 1 minute after intubation, then at every 1- minute intervals till first 5 minutes, and thereafter at 10 minutes and at 15 minutes after intubation. The descriptive statistics of data were expressed as mean and standard deviation. Independent samples t-test was used for comparison of mean values of the variables in both groups. The value of p&lt; 0.05 was considered as statistically significant. Results: There was a significant rise in heart rate and blood pressure after laryngoscopy and endotracheal intubation with acetaminophen (P group) as compared to the N group in which nalbuphine effectively reduced the tachycardia and hypertension. Conclusion: Acetaminophen has no significant effect on the prevention of hemodynamic changes due to intubation. Nalbuphine effectively reduces tachycardia and hypertension associated with laryngoscopy and endotracheal intubation.

Role of intravenous acetaminophen infusion for analgesia during active labour

Role of intravenous acetaminophen infusion for analgesia during active labour

Effectiveness of scheduled postoperative intravenous acetaminophen for colon cancer surgery pain

BackgroundClinical cases are often observed when patients are in need of repeated use of analgesic infusion to manage pain after colon cancer surgery. This paper investigates analgesic frequency as well as safety of postoperative intravenous (IV) acetaminophen in colon cancer surgery where epidural anesthesia is used.MethodsAmong patients who received epidural anesthesia during colon cancer surgery, one group of twenty eight (28) patients received acetaminophen while another group of patients (30) did not receive it. The groups were analyzed from the surgery day to two days after for the postoperative occurrence and frequency of liver dysfunction in relation to analgesic usage.ResultsThe patient group with acetaminophen infusion significantly reduced the amount of analgesic medication compared to the group without the treatment (p = 0.008). Furthermore there was a significantly larger number of patients in the group receiving acetaminophen treatment with the baseline increase of alanine aminotransferase (p = 0.043). In most of the cases, however, the rate of the increase is mild and the patients did not need medication and subsequently recovered quickly.ConclusionsScheduled IV infusion of acetaminophen after colon cancer surgey is concluded an effective method of pain control and alleviation of postoperative discomfort from the surgery day to two days after the surgery.

Effects of IV Acetaminophen on Core Body Temperature and Hemodynamic Responses in Febrile Critically Ill Adults: A Randomized Controlled Trial.

To determine the effects of IV acetaminophen on core body temperature, blood pressure, and heart rate in febrile critically ill patients. Randomized, double-blind, placebo-controlled clinical trial. Three adult ICUs at a large, urban, academic medical center. Forty critically ill adults with fever (core temperature, ≥ 38.3°C). An infusion of acetaminophen 1 g or saline placebo over 15 minutes. Core temperature and vital signs were measured at baseline and at 5-15-minute intervals for 4 hours after infusion of study drug. The primary outcome was time-weighted average core temperature adjusted for baseline temperature. Secondary outcomes included adjusted time-weighted average heart rate, blood pressure, and respiratory rate, along with changes-over-time for each. Baseline patient characteristics were similar in those given acetaminophen and placebo. Patients given acetaminophen had an adjusted time-weighted average temperature that was 0.47°C less than those given placebo (95% CI, -0.76 to -0.18; p = 0.002). The acetaminophen group had significantly lower adjusted time-weighted average systolic blood pressure (-17 mm Hg; 95% CI, -25 to -8; p < 0.001), mean arterial pressure (-7 mm Hg; 95% CI, -12 to -1; p = 0.02), and heart rate (-6 beats/min; 95% CI, -10 to -1; p = 0.03). Changes-over-time temperature, blood pressure, and heart rate outcomes were also significantly lower at 2 hours, but not at 4 hours. Among febrile critically ill adults, treatment with acetaminophen decreased temperature, blood pressure, and heart rate. IV acetaminophen thus produces modest fever reduction in critical care patients, along with clinically important reductions in blood pressure.

Acetaminophen-Induced Changes in Systemic Blood Pressure in Critically Ill Patients: Results of a Multicenter Cohort Study.

We sought to assess the incidence of acetaminophen-induced hypotension. Our secondary objectives were to describe systemic hemodynamic changes and factors associated with this complication. Prospective observational study. Three ICUs. Adult patients requiring IV acetaminophen infusion. Arterial pressure was monitored via an arterial catheter for 3 hours. Hypotension was defined as a decrease in the mean arterial pressure of greater than or equal to 15% compared with the baseline. Overall, 160 patients were included in this study. Eighty-three patients (51.9%) experienced acetaminophen-induced hypotension according to our definition. In patients with acetaminophen-induced hypotension, the nadir mean arterial pressure was 64 mm Hg (95% CI, 54-74). Hypotension was observed 30 minutes (95% CI, 15-71) after acetaminophen infusion. Changes in mean arterial pressure were closely correlated with decreases in the diastolic arterial pressure (r = 0.92) and to a lesser extent with changes in the pulse pressure (r = 0.18) and heart rate (r = 0.09). Changes in the body temperature were not correlated with changes in mean arterial pressure (r = 0.0002; p = 0.85). None of the patients' baseline characteristics (shock, use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, lactates, renal replacement therapy, chronic heart disease, and indication for acetaminophen infusion) or clinically relevant characteristics (baseline severity according to Logistic Organ Dysfunction score, need for vasopressors, use of antihypertensive agents, need for mechanical ventilation, or changes in the body temperature) were independently associated with acetaminophen-induced hypotension. Among patients with acetaminophen-induced hypotension, 29 (34.9%) required therapeutic intervention. Half of the patients who received IV injections of acetaminophen developed hypotension, and up to one third of the observed episodes necessitated therapeutic intervention. Adequately powered randomized studies are needed to confirm our findings, provide an accurate estimation of the consequences of acetaminophen-induced hypotension, and assess the pathophysiologic mechanisms involved.

Efficacy of Intravenous Infusion of Acetaminophen for Intrapartum Analgesia.

The intensity of pain experienced by women in labour, has been found to affect the progress of labour, foetal well-being and maternal psychology. Adverse effects associated with commonly used opioids for providing intrapartum analgesia have created a need for an alternative non-opioid drug. To evaluate the efficacy of an intravenous infusion of 1000 mg of acetaminophen as an intrapartum analgesic. The present prospective single-centre, single blind, placebo-controlled randomized interventional study was conducted in Department of Obstetrics and Gynaecology in Vardhaman Mahavir Medical College & Safdarjung Hospital over a period of six months from September 2014 to March 2015. After receiving the ethical clearance and written informed consent. The first 200 consecutive parturients fulfilling the inclusion criteria were recruited into the study. Women were then randomised to receive either intravenous 1000 mg (100ml) of acetaminophen (Group A, n=100) or 100 ml normal saline (Group B, n=100). Primary outcome assessed was effectiveness of acetaminophen to provide an adequate amount of analgesia, as measured by a change in Visual Analogue Scale (VAS) pain intensity score at various times after drug administration. Secondary outcomes measured were duration of labour, need for additional rescue analgesia and presence of adverse maternal or foetal effect. There was pain reduction at 1 and 2 hours in both groups (p<0.001). However, it was more significant in the acetaminophen group, especially at 1 hour. Duration of labour was shortened in both the groups, without any maternal and foetal adverse effects. Intravenous acetaminophen is an efficacious non-opioid drug for relieving labour pain without any significant maternal and foetal adverse effects.

Impact of intravenous acetaminophen therapy on the necessity of cervical spine imaging in patients with cervical spine trauma

ObjectiveWe evaluated a new hypothesis of acetaminophen therapy to reduce the necessity of imaging in patients with probable traumatic cervical spine injury. MethodsPatients with acute blunt trauma to the neck and just posterior midline cervical tenderness received acetaminophen (15mg/kg) intravenously after cervical spine immobilization. Then, all the patients underwent plain radiography and computerized tomography of the cervical spine. The outcome measure was the presence of traumatic cervical spine injury. Sixty minutes after acetaminophen infusion, posterior midline cervical tenderness was reassessed. ResultsOf 1 309 patients, 41 had traumatic cervical spine injuries based on imaging. Sixty minutes after infusion, posterior midline cervical tenderness was eliminated in 1 041 patients, none of whom had abnormal imaging. ConclusionPatients with cervical spine trauma do not need imaging if posterior midline cervical tenderness is eliminated after acetaminophen infusion. This analgesia could be considered as a diagnostic and therapeutic intervention.

Safety of Rapid Intravenous Infusion of Acetaminophen

Intravenous acetaminophen, Ofirmev®, is approved for management of mild to moderate pain, management of moderate to severe pain with adjunctive opioids, and reduction of fever. The product is supplied as a 100 mL glass vial. As stated in the prescribing information, it is recommended to be infused over 15 minutes. This recommendation is related to the formulation propacetamol, the prodrug to acetaminophen, approved in Europe, which caused pain on infusion, and data from the clinical development of acetaminophen. The objective of this retrospective chart review study was to show the lack of side effects of rapidly infusing intravenous acetaminophen. Charts of American Society of Anesthesiology (ASA) Class I–III ambulatory surgical patients who received only acetaminophen in the preoperative setting were reviewed for any infusion-related side effects. Using standard binomial proportion analyses and employing SAS/JMP software, all vital signs were analyzed for statistically significant changes between pre- and postinfusion values. One hundred charts were reviewed. Only one patient had pain on infusion, which lasted 10 seconds. No reported side effects or erythema was seen at the injection site. No infusions had to be slowed or discontinued. The median infusion time was 3:41 minutes. Of the vital signs monitored, only the systolic (P < 0.0001) and diastolic (P < 0.0099) blood pressures had statistically significant changes from pre- to postinfusion; however, they were of no clinical relevance. Acetaminophen can be administered as a rapid infusion with no significant infusion-related side effects or complications.

Tropisetron blocks analgesic action of acetaminophen: A human pain model study

Because the mechanism underlying the analgesic action of acetaminophen remains unclear, we investigated the possible interaction of acetaminophen with central serotonergic pathways. The effects of acetaminophen, tropisetron, the combination of both drugs, and saline on pain perception and central sensitization in healthy volunteers were compared. Sixteen healthy volunteers were included in this randomized, double-blind, placebo-controlled crossover study. Intracutaneous electrical stimulation (46.1 ± 19.1 mA) induced acute pain (numeric rating scale, 6 of 10) and stable areas of hyperalgesia and allodynia. Pain intensities and areas of hyperalgesia and allodynia were regularly assessed before, during, and after a 15-min infusion of acetaminophen, tropisetron, the combination of both drugs, and saline. Acetaminophen concentrations were measured to rule out any pharmacokinetic interaction. Both acetaminophen and tropisetron led to decreased pain ratings as compared to saline. However, when acetaminophen and tropisetron were administered simultaneously, the pain ratings were not affected. There was no significant difference in the evolution of the hyperalgesic and allodynic areas during the study period between the study groups ( P = .06 and P = .33, respectively). Acetaminophen serum levels were not significantly different when associated with tropisetron ( P = .063), although we observed a trend toward lower acetaminophen concentrations when both drugs were concurrently administered. In summary, while the combination of acetaminophen and tropisetron showed no analgesic action, each drug administered alone led to decreased pain ratings as compared to saline. In an electrically evoked human pain model, the combination of acetaminophen with tropisetron was free of any analgesic potential. However, when administered on its own, both acetaminophen and tropisetron were mildly analgesic.

Supra-additive effects of tramadol and acetaminophen in a human pain model

The combination of analgesic drugs with different pharmacological properties may show better efficacy with less side effects. Aim of this study was to examine the analgesic and antihyperalgesic properties of the weak opioid tramadol and the non-opioid acetaminophen, alone as well as in combination, in an experimental pain model in humans. After approval of the local Ethics Committee, 17 healthy volunteers were enrolled in this double-blind and placebo-controlled study in a cross-over design. Transcutaneous electrical stimulation at high current densities (29.6 ± 16.2 mA) induced spontaneous acute pain (NRS = 6 of 10) and distinct areas of hyperalgesia for painful mechanical stimuli (pinprick-hyperalgesia). Pain intensities as well as the extent of the areas of hyperalgesia were assessed before, during and 150 min after a 15 min lasting intravenous infusion of acetaminophen (650 mg), tramadol (75 mg), a combination of both (325 mg acetaminophen and 37.5 mg tramadol), or saline 0.9%. Tramadol led to a maximum pain reduction of 11.7 ± 4.2% with negligible antihyperalgesic properties. In contrast, acetaminophen led to a similar pain reduction (9.8 ± 4.4%), but a sustained antihyperalgesic effect (34.5 ± 14.0% reduction of hyperalgesic area). The combination of both analgesics at half doses led to a supra-additive pain reduction of 15.2 ± 5.7% and an enhanced antihyperalgesic effect (41.1 ± 14.3% reduction of hyperalgesic areas) as compared to single administration of acetaminophen. Our study provides first results on interactions of tramadol and acetaminophen on experimental pain and hyperalgesia in humans. Pharmacodynamic modeling combined with the isobolographic technique showed supra-additive effects of the combination of acetaminophen and tramadol concerning both, analgesia and antihyperalgesia. The results might act as a rationale for combining both analgesics.

Reduction of acetaminophen interference in glucose sensors by a composite Nafion membrane: demonstration in rats and man

Amperometric glucose sensors typically monitor the production of hydrogen peroxide generated in the course of the enzymatic oxidation of glucose. At the applied potential necessary to oxidize the peroxide produced, other species are also electroactive and contribute to the signal. Interference of ascorbate or urate has been effectively eliminated, but that resulting from the widely used analgesic acetaminophen is not. The aim of this work was to reduce this interference, which was found to be possible by introducing a membrane constructed of Nafion. We compared the in vitro sensitivity to acetaminophen of five Nafion sensors with that of five non-Nafion sensors with identical glucose sensitivity (2.0 +/- 0.4 vs 1.9 +/- 0.1 nA.mmol-1.l-1, NS): sensitivity to acetaminophen was 12.2 +/- 2.7 vs 30.8 +/- 6.3 nA.mmol-1.l-1, respectively (p < 0.05). These sensors were tested in rats by implanting in each animal one Nafion and one non-Nafion sensors. The in vivo sensitivity to glucose was similar (0.33 +/- 0.09 vs 0.30 +/- 0.05 nA.mmol-1.l-1, NS). The current generated by an acetaminophen infusion (plasma acetaminophen plateau = 140 +/- 10 mumol/l) was much decreased in the case of the Nafion sensor: 0.5 +/- 0.3 vs 2.0 +/- 0.7 nA, p < 0.05). Five Nafion sensors were implanted in the subcutaneous tissue of normal human volunteers who were given on oral dose of 500 mg acetaminophen.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of acetaminophen interference in glucose sensors by a composite Nafion membrane: demonstration in rats and man

Amperometric glucose sensors typically monitor the production of hydrogen peroxide generated in the course of the enzymatic oxidation of glucose. At the applied potential necessary to oxidize the peroxide produced, other species are also electroactive and contribute to the signal. Interference of ascorbate or urate has been effectively eliminated, but that resulting from the widely used analgesic acetaminophen is not. The aim of this work was to reduce this interference, which was found to be possible by introducing a membrane constructed of Nafion. We compared the in vitro sensitivity to acetaminophen of five Nafion sensors with that of five non-Nafion sensors with identical glucose sensitivity (2.0±0.4 vs 1.9±0.1 nA·mmol−1· 1−1, NS): sensitivity to acetaminophen was 12.2±2.7 vs 30.8±6.3 nA·mmol−1·1−1, respectively (p<0.05). These sensors were tested in rats by implanting in each animal one Nafion and one non-Nafion sensors. The in vivo sensitivity to glucose was similar (0.33±0.09 vs 0.30±0.05 nA·mmol−1·1−1, NS). The current generated by an acetaminophen infusion (plasma acetaminophen plateau=140±10 μmol/l) was much decreased in the case of the Nafion sensor: 0.5±0.3 vs 2.0±0.7 nA, p<0.05). Five Nafion sensors were implanted in the subcutaneous tissue of normal human volunteers who were given on oral dose of 500 mg acetaminophen. No change in the sensor current was observed, although plasma acetaminophen reached a peak (35±6 μmol/l) at 60 min and decreased by 50% at 180 min. In contrast, the current increased from 2.1±0.7 to 3.9±1.2 nA (p<0.05) at 60 min of a subsequent oral glucose tolerance test when plasma glucose concentration increased from 4.8±0.3 to 8.0±0.9 mmol/l. This paper provides the evidence that the presence of a Nafion membrane is a solution to acetaminophen interference in glucose sensing.

Glycoconjugates as noninvasive probes of intrahepatic metabolism: I. Kinetics of label incorporation with evidence of a common precursor UDP-glucose pool for secreted glycoconjugates

Conditions are described under which hepatic metabolism of administered labeled sugars can be monitored in the intact rat by measuring output of label from the liver in two secreted glycoconjugates derived from intracellular UDP-glucose, namely glucuronic acid linked to an administered drug (acetaminophen), and galactose secreted in glycoproteins. Rats with indwelling intrajugular catheters were given constant infusions of acetaminophen at nontoxic doses, and acetaminophen-glucuronide was isolated from rat urine by HPLC. When an unprimed continous infusion of [U- 14C]glucose or [1- 3H]galactose is begun during acetaminophen infusion, labeling of urinary acetaminophen-glucuronide attains a plateau with an apparent half-life of 2.1 h from labeled glucose as the 14C-donor, and 1.2 h from labeled galactose. The times required to attain steady-state are attributable either to formation or to hepatic secretion of the glucuronyl conjugate rather than to mixing in extracellular pools or to delays in renal excretion since the half-time of urinary excretion of intravenously injected acetaminophen-glucuronide is only 21 minutes. Consequently, the excreted glucuronide provides noninvasive evidence of the recent specific activity in the precursor pool of hepatic UDP-glucose feeding glucuronic acid. The second glycoconjugate used for comparison was galactose, isolated from the acute-phase plasma protein alpha 1-acid glycoprotein. This represents hepatic UDP-galactose labeling. Comparison of the labeling patterns of secreted galactose and glucuronic acid demonstrates that they are derived from the same intracellular pool of UDP-glucose. This is in contrast to the patterns of labeling of hepatic glycogen from (1- 3H) and [U- 14C]glucose which have been shown to diverge from those of secreted glucuronic acid.