Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Fentanyl”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMedDate not supplied

Addition of fentanyl to bupivacaine prolongs anesthesia and analgesia in axillary brachial plexus block.

BACKGROUND AND OBJECTIVES: To evaluate the analgesic and anesthetic effects of 40 mL bupivacaine 0.25%, 40 mL bupivacaine 0.25% plus fentanyl 2.5 microg/mL, and 40 mL bupivacaine 0.125% plus fentanyl 2.5 microg/mL for axillary brachial plexus block. METHODS: Sixty patients were randomly allocated to 3 groups and received axillary brachial plexus block with 40 mL bupivacaine 0.25% (group B), 40 mL bupivacaine 0.25% with fentanyl 2.5 microg/mL (group BF), or 40 mL bupivacaine 0.125% with fentanyl 2.5 microg/mL (group DBF). The onset times and the duration of sensory and motor blocks, duration of analgesia, hemodynamic parameters, and adverse events were noted. RESULTS: The mean duration of sensory block and analgesia were longer in group BF (10.1 hours and 20.9 hours) than group B (6.9 hours and 11.6 hours) and DBF (5.9 hours and 12.0 hours) (P < .01, P < .001, respectively). The mean duration of motor block was also longer in group BF (10.7 hours) than group B (4.9 hours) (P < .01). Only 2 patients experienced motor block in group DBF. The frequency of successful block was 35% in group DBF (P < .01). Hemodynamic parameters were similar in all groups. In group B, only 1 patient experienced dizziness. Nausea was observed in 1 patient in each fentanyl group. CONCLUSION: The addition of 100 microg/mL fentanyl to 0.25% bupivacaine almost doubles the duration of analgesia following axillary brachial plexus block when compared with 0.25% bupivacaine alone.

Adult↗
PubMedDate not supplied

Intrathecal fentanyl added to hyperbaric ropivacaine for cesarean delivery.

BACKGROUND AND OBJECTIVES: Hyperbaric ropivacaine produces adequate spinal anesthesia for cesarean delivery. Addition of opioid to local anesthetics improves spinal anesthesia. We assessed the effect of fentanyl added to hyperbaric ropivacaine for spinal anesthesia for cesarean delivery. METHODS: Fifty-nine healthy, full-term parturients scheduled for elective cesarean delivery under spinal anesthesia were randomly assigned in a double-blind fashion to receive either fentanyl 10 micro g or normal saline 0.2 mL added to 0.5% hyperbaric ropivacaine 18 mg. Characteristics of spinal block, intraoperative quality of spinal anesthesia, side effects, complete analgesia (time to first feeling of pain), and effective analgesia (time to first request of analgesics) were assessed. RESULTS: Duration of sensory block was prolonged in the fentanyl group (P <.05). Duration of motor block was similar in both groups. The quality of intraoperative analgesia was better in the fentanyl group (P <.05). Incidence of side effects did not differ between groups. Duration of complete analgesia (143.2 +/- 34.2 minutes v 101.4 +/- 21.4 minutes; P <.001) and effective analgesia (207.2 +/- 32.2 minutes v 136.3 +/- 14.1 minutes; P <.001) were prolonged in the fentanyl group. CONCLUSIONS: Adding fentanyl 10 micro g to hyperbaric ropivacaine 18 mg for spinal anesthesia for cesarean delivery improves intraoperative anesthesia and increases the analgesia in the early postoperative period.

Adult↗
PubMed2006

[No potentiation of fentanyl by use of transdermal buprenorphine in patients undergoing fast-track anesthesia for open-heart surgery].

OBJECTIVE: Simultaneous use of opioids with a different pharmacological profile may lead to unexpected prolongation of effects. In an open label study possible overhang in post-operative respiratory effects and vigilance was determined in a group of patients (n = 22) carrying a transdermal buprenorphine patch for at least 2 months for treatment of chronic pain, undergoing a fentanyl-based fast-track enflurane anesthetic technique for open-heart operation. Data was compared with another randomised group (n = 21) undergoing similar open-heart procedures with no other opioid than fentanyl on board. METHODS AND RESULTS: Following induction with fentanyl and a barbiturate, depth of anesthesia with enflurane (Fi 0.5) was guided using the bispectral index (BIS). Additional doses of fentanyl were given when blood pressure and/or heart-rate increased 20% above pre-induction levels. Early postoperative extubation was initiated once the cardiovascular system was stable and there were no signs of respiratory impairment. Following a similar time of operation and anesthesia and a similar total dose of fentanyl (0.69 mg +/- 0.23 SD versus 0.67 mg +/- 0.16 SD), postoperatively, there were no significant differences between the buprenorphine- and the control group regarding the time till extubation (25.2 min +/- 6.1 versus 33.3 min +/- 5.0) and the arterial blood gases under oxygen inhalation (paO2 136 torr +/- 48 SD versus 128 torr +/- 35 SD; paCO2 43.3 torr +/- 3.3 SD versus 41.9 torr +/- 1.2 SD and the post-anesthetic vigilance and recovery score (6.8 +/- 1.0 versus 7.5 +/- 0.8) 60 minutes after end of anesthesia. Contrary to the control group, there was a lower and significant (p < 0.01) incidence of PONV in patients with transdermal buprenorphine. CONCLUSION: Patients using a buprenorphine patch for the relief of chronic pain cannot be regarded as opioid naïve. Due to adaptive mechanisms and the development of tolerance, there is no prolongation of the respiratory depression induced by intraoperative fentanyl. Long-term use of transdermal buprenorphine does not lead to potentiation or prolongation of opioid effects in cardiac surgery patients.

Administration, Cutaneous↗
PubMed1994

[Effects of propofol and fentanyl on the baroreceptor reflex in geriatric patients].

OBJECTIVE: Increasing age and anaesthetics diminish the baroreflex response to acute changes in blood pressure. This study was designed to investigate the effects of propofol and the combination of propofol with fentanyl on the baroreflex activity in geriatric patients. METHODS: Baroreflex sensitivity was studied by the method of Smyth et al. in 10 elderly (72 +/- 6 yrs) and in 10 younger (48 +/- 6 yrs) patients. Nitroprusside (depressor test) and phenylephrine (pressor test) were used to induce changes in blood pressure of 20 mmHg each to alter the stimulation of the baroreceptor sites. Anaesthesia was induced with propofol, 2 mg x kg-1 b.w.m, and maintained by a continuous infusion of 12 mg x kg-1 x h-1 for 10 min and thereafter with 6 mg x kg-1 x h-1. Then a bolus of fentanyl, 7 micrograms x kg-1 b.w. was injected. Haemodynamic parameters and baroreflex activity were measured in the awake state, 10 min after induction of anaesthesia and 10 min after the administration of fentanyl. Plasma propofol concentrations were determined by HPLC 10 min after induction of anaesthesia with propofol and 10 min after injection of fentanyl. The slope of the linear regression changes in RR-interval [ms] per changes in systolic pressure [mmHg] was used as an index of the baroreflex sensitivity. RESULTS: In the awake state the depressor slopes were significantly reduced by 60% in the elderly patients when compared to the younger patients. In both groups propofol decreased reflex sensitivity by 38% and 41% respectively; this effect was enhanced by the addition of fentanyl in the younger patients, while there was no further effect in the elderly. The pressor slopes did not change significantly in both groups neither with propofol nor with the combination of fentanyl, but again reflex response was significantly less in the elderly patients. CONCLUSION: Our data demonstrate that in geriatric patients the baroreflex control of heart rate already is attenuated in the awake state. Propofol produces a further reduction in reflex sensitivity to an acute decrease in blood pressure; this effect is more pronounced in elderly patients as compared to younger individuals. Acute changes in posture or circulating blood volume during propofol anaesthesia may result in greater cardiovascular instability in older patients due to the greater impairment of circulatory control mechanisms.

Adult↗
PubMed2001

A randomized controlled trial of fentanyl for abortion pain.

OBJECTIVE: Our aim was to find out whether intravenous fentanyl was effective in reducing the pain of first-trimester abortion. STUDY DESIGN: This randomized controlled trial included 825 women attending a nonhospital abortion facility. Some women chose standard care. Women who did not choose standard care were randomly assigned to receive either 50 to 100 microg of fentanyl, a placebo, or no intervention. With SAS software and a mixed effects analysis of variance model with covariates, we compared mean pain scores of the fentanyl and placebo groups to detect a difference of at least 1 point on an 11-point pain scale. RESULTS: The mean pain score of the fentanyl group was 1.0 point less than that of the placebo group (95% confidence interval, 3.7-4.3) and 0.9 point less than that of the observational group (95% confidence interval, 4.7-5.1). This pain reduction was statistically significant, but the women who were studied wanted a 2-point reduction from fentanyl. CONCLUSION: Fentanyl, when compared with the placebo, reduced abortion pain by 1.0 point on an 11-point scale. This reduction was of questionable clinical significance and was less than desired by the women included in the study.

Abortion, Induced↗
PubMed2003

A one year health economic model comparing transdermal fentanyl with sustained-release morphine in the treatment of chronic noncancer pain.

A Markov model was constructed to simulate the resource use and health outcomes of one year of treatment comparing the fentanyl transdermal therapeutic system (fentanyl-TTS) with oral sustained-release (SR) morphine in outpatients with noncancer pain in Denmark. Effectiveness was assessed in terms of days of good pain control and days on initial treatment. Costs included those of baseline pain management, including breakthrough pain; co-medication costs; and control of adverse events. Fentanyl-TTS was more effective than SR-morphine in achieving good pain control (99 vs. 64 days, respectively) and the incremental cost-effectiveness of fentanyl-TTS was US dollars 10.26 per extra day of good pain control. Patients treated with fentanyl-TTS remained considerably longer on initial treatment compared with those treated with SR-morphine (166 days vs. 117 days, respectively). The results of this study suggest that fentanyl-TTS is a competitive therapeutic and economic choice for the treatment of chronic noncancer pain.

Administration, Cutaneous↗
PubMed1985

pH-dependent accumulation of fentanyl, lofentanil and alfentanil by beating guinea pig atria.

The influence of the pH of the incubation medium on the cellular accumulation of tritiated fentanyl, lofentanil, and alfentanil was investigated in isolated guinea pig atria. Fentanyl and lofentanil accumulated in atrial tissue up to about 30- and 50-fold, respectively. The amount of drug bound when equilibrium was attained was found to be dependent upon the pH of the medium. By plotting binding equilibria v. pH of the bath, curves were obtained which resembled titration curves. Half-maximal binding was attained at pH values close to the pKa values of fentanyl and lofentanil. Alfentanil was found to accumulate less. The uptake by the tissue was strongly proportional to the extracellular concentration. Atria equilibrated with fentanyl at pH 8.5 released the compound rapidly when exposed to a pH of 7.0, even in the continuous presence of fentanyl in the bath. The consequences of the findings for in vivo conditions are discussed with respect to a possible augmentation of the actions of fentanyl by respiratory acidosis.

Alfentanil↗
PubMed1988

Pulmonary kinetics of fentanyl and alfentanil in surgical patients.

The pulmonary kinetics of fentanyl and alfentanil were studied quantitatively in two groups of five and six surgical patients, respectively, after the induction of anaesthesia. A mixture of one of the opioids and indocyanine green was administered as a bolus. From measurements of the concentrations of the dye in plasma and the opioids in blood, central blood volume and the amount of drug which passed through the pulmonary circulation were calculated. The pulmonary release of fentanyl and alfentanil was calculated from the arterial-mixed venous blood concentration differences. Fentanyl 43.0-86.9% (median 70.9%) and 35.9-79.8% of alfentanil (median 58.6%) were sequestered by the lung on first passage of the opioid-containing blood through the pulmonary capillaries. During the following 14 min, fentanyl was released, apparently from two binding sites (T1/2fast: 0.22 (0.16-0.27) min; T1/2slow: 5.78 (3.65-13.86) min). Initially, there was a rapid release of alfentanil (T1/2: 0.28 (0.08-0.51) min). However, 1-3 min after injection, the arterial-mixed venous blood concentration differences of alfentanil disappeared, although considerable amounts of drug were still present in the lung of five of the six patients studied. It may be expected that a temporary pulmonary sequestration of fentanyl and alfentanil has considerable impact on the time course of their pharmacological effects, on the time necessary to reach their maximum effect and on the intensity and (in case of fentanyl) the duration of these effects.

Adult↗
PubMed1990

Site of action of fentanyl in inhibiting the pituitary-adrenal response to surgery in man.

To determine the site of action of fentanyl in attenuating the pituitary-adrenal response to surgery, we have measured serum concentrations of cortisol and growth hormone during and after a standardized surgical procedure in two groups of patients. One group received fentanyl 15 micrograms kg-1 i.v. immediately before the start of surgery; a second group received fentanyl 15 micrograms kg-1 i.v. together with corticotrophin releasing factor 100 micrograms i.v., growth hormone releasing hormone 100 micrograms i.v. and arginine vasopressin 10 units i.m. The concomitant administration of the releasing factors with the opioid resulted in a significantly greater serum concentration of cortisol 30, 60, 120 and 240 min after surgery commenced, compared with the group which received fentanyl alone. Similarly, the growth hormone response in the combined group was significantly greater than in the fentanyl-alone group 30 min after the start of surgery. We conclude that the inhibitory effect of fentanyl on surgically-induced secretion of pituitary hormone was mediated directly or indirectly via the hypothalamus.

Arginine Vasopressin↗
PubMed1992

Effect of fentanyl on ventilatory resistances during barbiturate general anaesthesia.

Fentanyl has been shown to increase the overall resistance to inspiratory flow of the ventilatory system (Rmax). Rmax is the sum of the airway resistance (Raw) and of the non-Newtonian resistance (delta R) which may result from the viscoelastic properties of the thoracic tissues, from inequalities of the regional time constants within the lung, or from both. A bronchoconstrictor challenge may increase the magnitude of variation in regional time constants. Thus, in order to describe the effect of fentanyl on the two components of Rmax, this study was performed, with the end-inflation occlusion method, during paralysis and mechanical ventilation in 10 normal men undergoing barbiturate anaesthesia for minor urological procedures. The patients were anaesthetized with methohexitone and paralysed with vecuronium. Before administration of fentanyl, delta R accounted for 56% of Rmax. Fentanyl 5 micrograms kg-1 elicited a significant increase in Rmax (+34.5%; P = 0.005) and a parallel increase in both Raw (+35.2%, P = 0.017) and delta R (+33.5%, P = 0.005). The increase in Raw, but not in delta R, was reversed by atropine, suggesting that the increase in these two components of Rmax was not linked. Thus fentanyl increased both components of Rmax, but the effects of fentanyl on Raw and delta R seemed to depend on different mechanisms.

Adult↗
PubMed1993

Effects of fentanyl on the rat aorta are mediated by alpha-adrenoceptors rather than by the endothelium.

We have assessed if fentanyl interacts with the endothelium to affect vessel tone. In the presence or absence of endothelium, fentanyl in concentrations greater than 10(-7) mol litre-1 decreased the sensitivity of the rat aortic rings to phenylephrine, but fentanyl in smaller concentrations had no significant effect. Rings, with or without endothelium, and pre-contracted by phenylephrine were relaxed by fentanyl, and this relaxation was not inhibited by the opioid receptor antagonist, naloxone. Pretreatment of the rings with either fentanyl or phentolamine protected alpha-adrenoceptors from block by the alpha-adrenoceptor antagonist, phenoxybenzamine. We conclude that, in the rat aorta, fentanyl-induced relaxation was mediated by alpha-adrenergic receptors, and that the endothelium modulated, but did not mediate, this relaxation.

Animals↗
PubMed1994

Comparison of desflurane and fentanyl-based anaesthetic techniques for coronary artery bypass surgery.

We have compared, in 51 ASA II and III patients undergoing coronary artery bypass surgery, an inhaled anaesthetic technique based on desflurane, supplemented with low-dose (10 micrograms kg-1) fentanyl, with an i.v. technique using high-dose (50 micrograms kg-1) fentanyl with midazolam for induction. Satisfactory records were available for analysis in 50 patients. There were no differences between groups in operating time, cardiopulmonary bypass time, aortic cross-clamp time or duration of stay in the intensive care unit after surgery. Desflurane maintained mean systemic arterial pressure at the awake level during incision and sternotomy (end-tidal concentrations 3.7% and 4.6%, respectively) but decreased it significantly at all other times. With fentanyl, mean systemic arterial pressure was unchanged from awake values during induction and laryngoscopy but increased significantly at incision and sternotomy by 8% and 12.8%, respectively, to exceed the desflurane group at sternotomy by 20 mm Hg (P < 0.001). With desflurane, heart rate remained at 60-67 beat min-1 at all times before cardiopulmonary bypass. This was always lower than the fentanyl group by 5-15 beat min-1 and the difference was significant at induction, during skin preparation and before aortic cannulation. In comparison with the desflurane group, cardiac index was significantly greater in the fentanyl group at induction, laryngoscopy and during skin preparation, but was significantly less before aortic cannulation. The need for vasodilator intervention was significantly more common in the fentanyl group before, during and after cardiopulmonary bypass and for beta adrenoceptor block before cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

Effects of fentanyl, nitrous oxide, or both, on baroreceptor reflex regulation in the cat.

We have investigated the effects of fentanyl, nitrous oxide, or both, on carotid sinus baroreceptor reflexes in cats during basal chloralose anaesthesia. The bilaterally isolated carotid sinuses were perfused at prevailing systemic arterial pressure or at predetermined levels of pump-controlled pulsatile pressures of 50-200 mm Hg in steps of 25 mm Hg. Other major baroreceptor sites were denervated by bilateral vagotomy. Fentanyl decreased arterial pressure dose-dependently when the carotid sinuses were perfused at prevailing systemic arterial pressure and when the perfusion pressure was controlled artificially. High-dose fentanyl reduced significantly baroreceptor reflex responses in the sinus perfusion pressure range 50-125 mm Hg. Nitrous oxide increased arterial pressure in the carotid sinus perfusion range 75-125 mm Hg. There was no interaction between nitrous oxide and fentanyl for baroreceptor reflex responses. Our results indicated that baroreceptor reflexes, with and without nitrous oxide, were well preserved by moderate doses of fentanyl while high doses of fentanyl depressed baroreceptor reflexes.

Analgesics, Opioid↗
PubMed1997

Comparison of the effects of ketamine-midazolam with those of fentanyl-midazolam on cortical somatosensory evoked potentials during major spine surgery.

Cortical somatosensory evoked potentials (CSEP) allow monitoring of spinal cord function during surgery. Ketamine has been shown to enhance CSEP amplitude, but there is no previous study comparing its effects with those of other anaesthetic regimens. Therefore, we have compared the effects of ketamine with those of fentanyl, both combined with midazolam, on CSEP monitoring during major spine surgery. Twenty patients with normal preoperative CSEP were allocated randomly to a ketamine or fentanyl group. Anaesthesia was induced with ketamine 3 mg kg-1 or fentanyl 6 micrograms kg-1 i.v., and midazolam 0.3 mg kg-1 i.v in both groups, and maintained with continuous i.v infusion of ketamine 2 mg kg-1 h-1 or fentanyl 3 micrograms kg-1 h-1, combined in both groups with midazolam 0.15 mg kg-1 h-1 and 60% nitrous oxide in oxygen. CSEP were elicited by tibial posterior nerve stimulation and measured P1 and N1 latencies, and P1-N1 amplitude, CSEP were recorded before and after induction, at 15 min, 1 and 2 h after induction, during skin closure and after removal of nitrous oxide. Both groups were comparable in characteristics, duration of surgery, mean arterial pressure and temperature. CSEP latencies were not significantly affected in either group. CSEP amplitude decreased significantly over time in the fentanyl group (from mean 2.02 (SEM 0.41) to 0.95 (0.17) microV, P < 0.05), but not in the ketamine group (from 1.33 (0.36) to 1.05 (0.31) microV, ns). Nevertheless, we did not observe any significant differences in amplitudes or latencies between the two groups. The delay in obtaining the first voluntary postoperative motor response was significantly greater in the ketamine group (170 (54) vs 55 (17) min, P < 0.01). Both ketamine and fentanyl allowed us to obtain reliable CSEP during major spine surgery, and there were no significant difference between these two anaesthetic regimens for CSEP monitoring, but a longer delay for voluntary postoperative motor assessment was observed in the ketamine group.

Adult↗
PubMed1998

The CYP 3A4 inhibitor itraconazole has no effect on the pharmacokinetics of i.v. fentanyl.

We studied 10 healthy volunteers given itraconazole 200 mg orally, once daily or placebo for 4 days in a crossover study. i.v. fentanyl 3 micrograms kg-1 was given on day 4. Plasma concentrations of fentanyl were measured by radioimmunoassay and ventilatory frequency and peripheral arteriolar oxygen saturation were also measured. Fentanyl-induced subjective effects (drowsiness, itching, nausea, performance, feeling of drug effect) were measured by visual analogue scales. The pharmacokinetics and pharmacodynamics of fentanyl were similar after both itraconazole and placebo. Thus although itraconazole is a strong inhibitor of the cytochrome 3A enzymes responsible for metabolism of fentanyl in vitro, it did not affect the i.v. pharmacokinetics of fentanyl in humans.

Adult↗
PubMed1999

Placental transfer of fentanyl in early human pregnancy and its detection in fetal brain.

We have investigated the transfer of fentanyl across the early human placenta in 38 women (8-14 weeks' gestation) undergoing termination of pregnancy. After administration of a bolus dose of fentanyl 2 micrograms kg-1 at induction of anaesthesia, maternal blood n = 38), placenta (n = 38), amniotic fluid (n = 38) and fetal brain (n = 7) samples were collected and assayed for fentanyl by radioimmunoassay. Fentanyl was detected in all placental and fetal brain samples but not in amniotic fluid. There was a rapid decrease in fentanyl concentrations in maternal serum after the bolus but placental concentrations had not started to decline 30 min later. There was no difference in placental drug concentrations at different gestational ages. These data suggest that there is rapid transfer of fentanyl to the fetus in early pregnancy and that the drug remains in fetal tissue for some time after the initial dose is given to the mother.

Abortion, Therapeutic↗
PubMed2000

Fentanyl reduces infarction but not stunning via delta-opioid receptors and protein kinase C in rats.

Langendorff rat hearts were used (i) to examine whether fentanyl reduces stunning, infarction or both, and (ii) to investigate if this protection is mediated by delta-opioid receptors and/or protein kinase C (PKC). In the stunning study, hearts were subjected to global ischaemia (20 min) and reperfusion. This did not produce infarction. Postischaemic mechanical function was measured in hearts treated with or without fentanyl (740 nM). Fentanyl did not affect postischaemic mechanical function. In the infarction study, the left anterior descending coronary artery was occluded for 35 min and infarct size was assessed by triphenyltetrazolium chloride staining. Hearts in the control group exhibited an infarct zone/area at risk (I/R) of 39 (SEM 5)%, whereas the I/R for the fentanyl group was 13 (2)%. When the hearts were treated with a delta-opioid receptor antagonist (naltrindole 1 nM) or a PKC inhibitor (chelerythrine 2 microM), the effect of fentanyl was abolished, with I/R of 37 (1) and 36 (2)% respectively. In our model, we conclude that fentanyl protects against infarction but not against stunning, and that the limitation of ischaemic injury is mediated by both delta-opioid receptors and PKC.

Analgesics, Opioid↗
PubMed2007

Fentanyl HCl iontophoretic transdermal system (ITS): clinical application of iontophoretic technology in the management of acute postoperative pain.

The fentanyl HCl iontophoretic transdermal system (fentanyl ITS) is a novel patient-controlled analgesia (PCA) system that has been approved in the USA and Europe for the management of acute, moderate-to-severe postoperative pain. This system extends the applicability of transdermal drug delivery to acute pain management, allowing patients to self-administer pre-programmed doses of fentanyl non-invasively through the use of iontophoretic technology. Iontophoresis is the process by which an electric current is used to drive ionized drug molecules across the skin and into the systemic circulation. Results of a recent US clinical trial found the fentanyl ITS to provide pain control equivalent to a standard regimen of morphine i.v. PCA, with a similar incidence of opioid-related adverse events. The fentanyl ITS may offer a number of clinical advantages over existing PCA modalities. Its method of drug delivery avoids the risk of complications from needle-related injuries and infection, and its pre-programmed electronics eliminate the potential for manual programming errors and excessive dosing. In addition, the compact size of the system could enable greater patient mobility following surgery. The fentanyl ITS has the potential to become a valuable option in the management of acute postoperative pain.

Acute Disease↗