OBJECTIVE: To compare the effects of different concentrations of ropivacaine femoral nerve block on postoperative pain and early exercise fllowing total knee arthroplasty(TKA). METHODS: A total of 90 patients who underwent primary TKA between September 2022 and February 2023 were consecutively enrolled in this study. The cohort consisted of 34 males and 56 females, with a mean age of (66.66±7.03) years old. According to different concentrations of ropivacaine, patients were divided into 0.1% group, 0.2% group and 0.4% group, with 30 patients in each group. The age, gender, body mass index(BMI), American Society of Aneshesiologists(ASA) grade, operation time, anesthesia time, tourniquet using time, Post Anesthesia care unit(PACU) stay duration, ambulation time, first reaching to Bromage 0 grade time, visual analogue scale(VAS), hospitalization period and postoperative adverse reactions were compared among the three groups. RESULTS: All 90 patients were followed up for an average of (31.56±5.62) days, and no postoperative adverse reactions occurred. There were no significant differences among the three groups in terms of age, gender, BMI, ASA classification, operation time, anesthesia time, tourniquet application time, PACU stay duration, and hospitalization period (P>0.05). Significant differences were observed in VAS scores at 1, 2, 4, 6, and 12 hours post-operation among the three groups (P<0.05). Additionally, significant variations were noted in ambulation time and the first reaching to Bromage level 0 time among the three groups (P<0.05). In terms of postoperative pain, the VAS of the 0.1% group at 1, 2, 4, 6, and 12 hours after surgery(1.93±0.52), (2.57±0.77), (3.10±0.71), (3.10±0.71), (3.07±0.45) points were higher than those of the 0.4% group (1.57±0.50), (2.10±0.55), (2.23±0.57), (2.47±0.73), (2.50±0.57) points, and the differences were statistically significant (P<0.05);the VAS of the 0.1% group at 4, 6, and 12 hours after surgery were higher than those of the 0.2% group (2.43±0.57), (2.53±0.57), (2.63±0.56) points, and the differences were statistically significant (P<0.05);there was no statistically significant difference in VAS between the 0.2% group and the 0.4% group (P>0.05). In terms of early postoperative mobility, the time to ambulation time (8.30±2.76) h and the time to achieve the first Bromage grade 0 (6.13±2.18) h were significantly prolonged in the 0.4% group compared to both the 0.1% group (6.93±1.76) h, (4.17±1.18) h and the 0.2% group (6.53±1.59) h, (4.87±1.53) h. No statistically significant differences were observed between the 0.1% and 0.2% groups (P>0.05). CONCLUSION 0.2% ropivacaine femoral nerve block can effectively reduce postoperative pain after TKA and can perform early exercise earlier.
Humans ; Male ; Female ; Ropivacaine/administration & dosage* ; Arthroplasty, Replacement, Knee/adverse effects* ; Aged ; Nerve Block/methods* ; Femoral Nerve/drug effects* ; Middle Aged ; Pain, Postoperative/drug therapy* ; Anesthetics, Local/administration & dosage* ; Amides

OBJECTIVETo compare the postoperative analgesia efficacy, rehabilitation parameters and complication between multimodal analgesia and traditional analgesia after radical gastrectomy for gastric cancer patients.

METHODSPatients with gastric cancer who underwent surgery in our hospital from October 2016 to December 2016 were enrolled in this prospective study. According to the non-randomized method, patients were assigned to multimodal analgesia group(n=32) and traditional analgesia group(n=33) in gastric cancer treatment team A and B in Department of Gastrointestinal Surgery, West China Hospital, Sichuan University. The treatment measures of group A were as follows: (1) The ratio of 1/1 diluted ropivacaine (100 mg, 10 ml) was infiltrated around the incision before abdomen closure, with incision sutured layer by layer. (2) Parecoxib sodium (40 mg) was injected intravenously every 12 hours after operation for 5 days. (3) Oxycodone-acetaminophen tablet was given orally on the first day or the second day after operation, 50 mg twice a day. (4) Patient-controlled analgesia was not used after operation. Patients in group B received direct suture of incision and patient-controlled analgesia. The pain score, postoperative rehabilitation and 30-day postoperative complications were collected and analyzed.

RESULTSMultimodal analgesia group had lower pain scores at 1 d (4.8±0.9), 2 d (4.3±1.0), 3 d (2.9±0.8), 4 d (2.4±0.7) and 5 d (1.7±0.7) after surgery, as compared to traditional analgesia group (5.9±0.9, P=0.000), (5.1±0.7, P=0.001), (3.9±0.8, P=0.000), (3.0±0.6, P=0.000), (2.6±0.7, P=0.000), with significant difference. Postoperative hospital stay [(8.2±1.6) days vs. (10.6±2.2) days, P=0.000], time to ambulation [(47.5±13.8) days vs. (66.2±16.8) days, P=0.000], time to first flatus [(76.4±25.2) days vs. (120.0±29.9) days, P=0.000], time to first defecate [(117.3±42.2) days vs. (159.7±30.7) days, P=0.000] and time to first fluid diet [(83.8±21.6) days vs. (141.9±33.9) days, P=0.000] in the multimodal analgesia group were significantly shorter than those in the traditional analgesia group. There was no significant difference between the two groups with respect to 30-day postoperative complication rate(9.4% vs. 9.1%, P=1.000).

CONCLUSIONSMultimodal analgesia can significantly reduce the postoperative pain and is beneficial to rehabilitation, meanwhile it does not increase the risk of postoperative complications. Multimodal analgesia is safe and effective for gastric cancer patients undergoing radical gastrectomy.

Acetaminophen ; administration & dosage ; therapeutic use ; Amides ; administration & dosage ; therapeutic use ; Analgesia, Patient-Controlled ; China ; Comparative Effectiveness Research ; Defecation ; Drug Combinations ; Eating ; Flatulence ; Gastrectomy ; rehabilitation ; Humans ; Isoxazoles ; administration & dosage ; therapeutic use ; Length of Stay ; statistics & numerical data ; Oxycodone ; administration & dosage ; therapeutic use ; Pain Management ; methods ; Pain, Postoperative ; drug therapy ; Postoperative Complications ; Prospective Studies ; Recovery of Function ; drug effects ; Stomach Neoplasms ; surgery ; Surgical Wound ; rehabilitation ; therapy ; Suture Techniques ; Treatment Outcome ; Walking

OBJECTIVETo investigate the effect of a single dose of ropivacaine combined with sufentanilfor thoracic paravertebral block (TPVB) on pain and enhanced recovery after surgery (ERAS) in patients undergoing video-assisted thoracosopic surgery.

METHODSSixty patients undergoing video-assisted thoracosopic surgery were randomly divided into three groups to receive intravenous combined general anesthesia (group C), a single dose of ropivacainefor thoracic paravertebral block before surgery combined with intravenous and general anesthesia(group T), or a single dose of ropivacaineand sufentanilfor thoracic paravertebral blockcombined with intravenous and general anesthesia (group T). None of the patients used postoperative analgesia pump, and tramadol hydrochoride injection (100 mg) was given in cases with NRS scores > 4 after the surgery. The data were recorded including analgesics used for nerve block before the operation, intravenous dosage of sufentanilduring operation, total dose of sufentanilused (intravenous+nerve block), intravenous remifentanil dose during operation, NRS scores at 4, 6, 24, 48 h after the surgery, rescue analgesia in the first postoperative 24 h after surgery, ICU stay and hospital stay after the surgery.

RESULTSCompared with those in group C, the intravenous sufentanildose, total sufentanildose, intravenous remifentanildose during operation, NRS scores at 4 and 6, 24 h, and ICU stay and hospital stay after the surgery were significantly decreased in groups Tand T(P<0.05). The total dose of opioids during the operation and NRS scores at 4 and 6 h were significantly lower in group Tthan in group T(P<0.05), but the total dose of sufentanil, ICU stay and hospital stay were simialr between the two groups.

CONCLUSIONA single dose of ropivacaine combined with sufentanilfor thoracic paravertebral blockbefore surgery can reduce the total dose opioids, produce the optimal analgesic effect, and promote postoperative recovery of the patients.

Amides ; administration & dosage ; therapeutic use ; Analgesics, Opioid ; therapeutic use ; Anesthesia, General ; Anesthetics, Intravenous ; therapeutic use ; Humans ; Injections ; Nerve Block ; methods ; Pain Management ; Pain Measurement ; Pain, Postoperative ; Piperidines ; therapeutic use ; Postoperative Period ; Sufentanil ; therapeutic use ; Thoracic Surgery, Video-Assisted

PURPOSE: This study examined the sparing effect of sufentanil on the median effective concentration (EC50) of epidural ropivacaine in elderly patients undergoing elective transurethral resection of prostate (TURP). MATERIALS AND METHODS: This was a prospective randomized double-blind dose-response study. Fifty eight elderly patients with American Society of Anesthesiologists physical status I-II who were scheduled for TURP surgery under epidural anesthesia were randomly allocated to a group receiving 15 mL of ropivacaine (group R) or a group receiving ropivacaine plus 5 microg of sufentanil (group RS). The concentration of ropivacaine was determined by a Dixon's up-and-down sequential allocation. The first participant received 0.3% of ropivacaine in both groups and subsequent concentrations were determined by the response of the previous patient in the same group. The EC50 of epidural ropivacaine was analyzed using the Dixon and Massey method. RESULTS: The EC50 of ropivacaine during TURP surgery was 0.186% (95% confidence interval, 0.173-0.200%) in group R, and 0.136% (95% confidence interval, 0.127-0.144%) in group RS (p<0.01). No differences in Bromage scale of motor block examination and the onset time of sensory block were observed. CONCLUSION: Administration of 5 microg of epidural sufentanil caused a 37% reduction in the EC50 of epidural ropivacaine in elderly patients who underwent TURP surgery. Thus, sufentanil addition during surgery of TURP can decrease the dose of ropivacaine anesthesia required.
Aged ; Aged, 80 and over ; Amides/*administration & dosage ; Anesthesia, Epidural/*methods ; Anesthetics, Local/*administration & dosage ; Dose-Response Relationship, Drug ; Double-Blind Method ; Humans ; Male ; Middle Aged ; Pain Measurement ; Prospective Studies ; Sufentanil/*administration & dosage ; *Transurethral Resection of Prostate ; Treatment Outcome

OBJECTIVETo evaluate the efficacy of continuous femoral block on the postoperative analgesia and functional recovery after total knee arthroplasty (TKA).

METHODSTwo hundreds and eighty patients who underwent TKA were randomized into two groups:the group receiving continuous femoral block (CFNB) and the group receiving patient controlled intravenous analgesia (PCIA), each group included 140 participants. Femoral nerve block with ropivacaine by ultrasonic guidance was performed in group CFNB and group PCIA were administrated with patient controlled intravenous analgesia. Numerical rating scale (NRS) scores at rest and in motion at 24, 48, 72 h, 3, 6 and 12 months postoperatively, also the NRS scores at hospital discharge were recorded. The incidence of moderate-severity pain, as well as the degree of knee flexion and the WOMAC scores at 3, 6 and 12 months after surgery were analyzed. The rescue analgesic administration and analgesia-related adverse effects were also recorded. Data were expressed as mean± standard deviation (SD) for normally distributed continuous variables and total number (percent frequency) for categorical variables. If non-normally distributed, data were expressed median inter-quartile range. Student's t-test, Wilcoxon rank test were used to compare results for continuous variables, when appropriate. Chi-square test was used to compare results for categorical variable, Fisher exact test was used for categorical variables when the number of event was less than 5.

RESULTSNRS scores of group CFNB in motion was 3 (3-4) at discharge time, and 3 (2-4), 3 (2-3) at 3 months and 6 months postoperatively, while the scores of group PCIA was 4 (4-4), 3 (3-4), 3 (3-4), respectively. And at rest, NRS scores of group CFNB was 3 (2-3), 1 (1-2), 1 (1-1) at discharge time, and 3, 6 months postoperatively. Compared with group PCIA, NRS scores in motion of group CFNB at discharge time (Z=-5.174, P<0.05) and 3 months (Z=2.308, P=0.021), as well as 6 months postoperatively (Z=-2.495, P=0.013), were significantly lower,also for the NRS scores at rest (Z=-2.405, P=0.016; Z=-4.360, P<0.05; Z=-9.268, P<0.05). The degree of knee flexion of group CFNB at 3 and 6 months postoperatively was 92 (88-97), 103 (99-106), while the degree of knee flexion of group PCIA was 89 (86-95), 100 (97-105); the WOMAC scores of group CFNB at 3 and 6 months postoperatively was 21 (18-26), 18 (16-22), while the scores of group PCIA was 24 (20-27), 21 (17-24). WOMAC scores of group CFNB was lower compared with group PCIA at 3 (Z=-2.467, P=0.014) and 6 (Z=-2.537, P=0.011) months postoperatively while the degree of knee flexion of group CFNB was higher (Z=-2.175, P=0.030; Z=-2.471, P=0.013). Moreover, the frequency of bolus and frequency of rescue of group CFNB was 2.3 and 0.6, while the frequency of group PCIA was 2.6 and 1.1, the frequency of bolus and frequency of rescue were lower in group CFNB (t=-2.984, P=0.003; t=-3.213, P=0.002). The incidence of adverse events such muscle weakness of low limbs,nausea and vomiting were similar in two groups (P>0.05).

CONCLUSIONCFNB can alleviate the postoperative pain after TKA with safety, help improving the short-middle-term functions of knee and quality of patients' lives.

Amides ; administration & dosage ; therapeutic use ; Analgesia ; methods ; Analgesia, Patient-Controlled ; Analgesics ; administration & dosage ; therapeutic use ; Arthroplasty, Replacement, Knee ; Femoral Nerve ; Femur ; Humans ; Knee Joint ; Nerve Block ; Pain, Postoperative ; drug therapy ; Postoperative Period ; Recovery of Function

BACKGROUNDSpinal anesthesia is considered as a reasonable anesthetic option in lower abdominal and lower limb surgery. This study was to determine the dose-response of intrathecal ropivacaine in patients with scarred uterus undergoing cesarean delivery under combined spinal-epidural anesthesia.

METHODSSeventy-five patients with scarred uterus undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this randomized, double-blinded, dose-ranging study. Patients received 6, 8, 10, 12, or 14 mg intrathecal hyperbaric ropivacaine with 5 μg sufentanil. Successful spinal anesthesia was defined as a T4sensory level achieved with no need for epidural supplementation. The 50% effective dose (ED50) and 95% effective dose (ED95) were calculated with a logistic regression model.

RESULTSED50and ED95of intrathecal hyperbaric ropivacaine for patients with scarred uterus undergoing cesarean delivery under combined spinal-epidural anesthesia (CSEA) were 8.28 mg (95% confidence interval [CI]: 2.28-9.83 mg) and 12.24 mg (95% CI: 10.53-21.88 mg), respectively.

CONCLUSIONWhen a CSEA technique is to use in patients with scarred uterus for an elective cesarean delivery, the ED50and ED95of intrathecal hyperbaric ropivacaine along with 5 μg sufentanil were 8.28 mg and 12.24 mg, respectively. In addition, this local anesthetic is unsuitable for emergent cesarean delivery, but it has advantages for ambulatory patients.

Adult ; Amides ; administration & dosage ; therapeutic use ; Anesthesia, Epidural ; methods ; Anesthesia, Spinal ; methods ; Cesarean Section ; methods ; Cicatrix ; Dose-Response Relationship, Drug ; Female ; Humans ; Pregnancy ; Sufentanil ; administration & dosage ; therapeutic use ; Uterus ; pathology

BACKGROUNDLowering intraocular pressure (IOP) is currently the only therapeutic approach in primary open-angle glaucoma. and the fixed-combination medications are needed to achieve sufficiently low target IOP. A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China. In this study, we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.

METHODSIn this multicenter, randomized, double-masked, parallel controlled study, patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1:1 ratio at 11 Chinese ophthalmic departments. Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03% bimatoprost and 0.5% timolol (followed by vehicle for masking) once daily at 19:00 P.M. and concurrent treatment was 0.03% bimatoprost followed by 0.5% timolol once daily at 19:00 P.M. The primary efficacy variable was change from baseline in mean diurnal intraocular pressure (IOP) at week 4 visit in the intent-to-treat (ITT) population. Primary analysis evaluated the non-inferiority of bimatoprost/ timolol fixed combination to concurrent with respect to the primary variable using a confidence interval (CI) approach. Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95% CI for the between-treatment (bimatoprost/timolol fixed combination minus concurrent) difference was ≤ 1.5 mmHg. Adverse events were collected and slit-lamp examinations were performed to assess safety. Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher's exact test.

RESULTSOf the enrolled 235 patients, 121 patients were randomized to receive bimatoprost/timolol fixed combination and, 114 patients were randomized to receive concurrent treatment. At baseline the mean value of mean diurnal IOP was (25.20 ± 3.06) mmHg in the bimatoprost/timolol fixed combination group and (24.87 ± 3.88) mmHg in the concurrent group. The difference between the treatment groups was not statistically significant. The mean change from baseline in mean diurnal IOP (± standard deviation) in the bimatoprost/timolol fixed combination group was (-9.38 ± 4.66) mmHg and it was (-8.93 ± 4.25) mmHg in the concurrent group (P < 0.01). The difference between the two treatment groups (bimatoprost/timolol fixed combination minus concurrent) in the change from baseline of mean diurnal IOP was -0.556 mmHg (95% CI: -1.68, 0.57, P = 0.330). The upper limit of the 95% CI was less than 1.5 mmHg, the predefined margin of non-inferiority. Adverse events occurred in 26.4% (32/121) of the bimatoprost/timolol fixed combination patients and 30.7% (35/114) of the concurrent patients. The most frequent adverse event was conjunctival hyperemia, which was reported as treatment related in 16.5% (20/121) in the bimatoprost/timolol fixed combination group and 18.4% (21/114) in the concurrent group (P > 0.05).

CONCLUSIONSBimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components. Safety profiles were similar between the treatment groups.

Adolescent ; Adult ; Aged ; Amides ; administration & dosage ; adverse effects ; therapeutic use ; Bimatoprost ; Cloprostenol ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Glaucoma, Open-Angle ; drug therapy ; Humans ; Male ; Middle Aged ; Ocular Hypertension ; drug therapy ; Timolol ; administration & dosage ; adverse effects ; therapeutic use ; Young Adult

BACKGROUNDContinuous interscalene nerve block (CISB) is considered to be the most effective method for postoperative analgesia after shoulder surgery with prolonged severe pain. This study was performed to evaluate the minimum effective background infusion rate and the effective background infusion rate of ropivacaine 0.2% for CISB after arthroscopic rotator cuff repair surgery in 95% of patients.

METHODSPatients scheduled for arthroscopic rotator cuff repair surgery under general anesthesia at Peking University Third Hospital were prospectively enrolled from December 2011 to May 2012. Preoperatively, an interscalene catheter (ISC) was placed under the guidance of ultrasound and nerve stimulation in each patient. Consecutively, 30 patients with successful nerve block were included. A continuous infusion of ropivacaine 0.2% with a 5 ml patient-controlled bolus available hourly was started at postoperative anesthesia care unit (PACU) after completion of surgery. The initial background infusion rate was 6 ml/h, which was subsequently varied for each consecutive patient according to the analgesic effects of the previous one. The minimum effective background rate was determined using the Dixon and Massey up-and-down method. The effective background rate in 95% of patients was calculated using isotonic analysis.

RESULTSThe minimum effective background rate based on the Dixon and Massey up-and-down method was 2.8 ml/h (95% CI, 2.3-3.3 ml/h). The effective background rate in 95% of patients calculated with the isotonic regression analysis was 4.4 ml/h (95% CI, 3.8-6.5 ml/h).

CONCLUSIONThe effective background rate for patient-controlled interscalene brachial plexus analgesia after shoulder surgery in 50% and 95% of the patients was 2.8 and 4.4 ml/h, respectively.

Adult ; Aged ; Amides ; administration & dosage ; therapeutic use ; Analgesia, Patient-Controlled ; methods ; Brachial Plexus ; surgery ; Female ; Humans ; Male ; Middle Aged ; Pain, Postoperative ; drug therapy ; Prospective Studies ; Rotator Cuff ; surgery

PURPOSE: To evaluate the effects of a bimatoprost/timolol fixed combination (BTFC) and a latanoprost/timolol fixed combination (LTFC) on diurnal intraocular pressure (IOP) and anterior ocular parameters in healthy subjects. METHODS: We enrolled 58 healthy subjects in this prospective clinical study. Thirty subjects were treated with BTFC and 28 subjects were treated with LTFC. IOP was measured every 2 hours except from 01:00 and 05:00. Axial length, corneal curvature, and anterior chamber depth were obtained using the IOL master at baseline and 24 hours later. Adverse events were assessed by patient interview and by slit lamp examination. RESULTS: The largest difference in IOP between treated and untreated eyes 8 hours after instillation was 1.67 mmHg in the BTFC group (p < 0.001). The largest difference in IOP between treated and untreated eyes 10 hours after instillation was 1.93 mmHg in the LTFC group (p < 0.001). For anterior ocular parameters such as axial length, corneal curvature, anterior chamber depth at baseline and 24 hours after instillation, there were no significant differences between the baseline and 24-hour values in either the BTFC or LTFC group. The most frequently occurring adverse event was conjunctival hyperemia, which was found in 33.3% (n = 10) of the BTFC group and 25.0% (n = 7) of the LTFC group (p = 0.486). CONCLUSIONS: BTFC and LTFC provided a significant reduction in IOP from baseline without changing any anterior ocular parameters. Our results provide a reference for monocular trials to assess the effect of eye drops in a clinical condition.
Adult ; Aged ; Aged, 80 and over ; Amides/*administration & dosage ; Antihypertensive Agents/administration & dosage ; Circadian Rhythm/*physiology ; Cloprostenol/administration & dosage/*analogs & derivatives ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Glaucoma, Open-Angle/drug therapy/*physiopathology ; Healthy Volunteers ; Humans ; Intraocular Pressure/drug effects/*physiology ; Male ; Middle Aged ; Ophthalmic Solutions ; Prospective Studies ; Prostaglandins F, Synthetic/*administration & dosage ; Timolol/*administration & dosage ; Tonometry, Ocular ; Treatment Outcome

PURPOSE: To evaluate the effects of a bimatoprost/timolol fixed combination (BTFC) and a latanoprost/timolol fixed combination (LTFC) on diurnal intraocular pressure (IOP) and anterior ocular parameters in healthy subjects. METHODS: We enrolled 58 healthy subjects in this prospective clinical study. Thirty subjects were treated with BTFC and 28 subjects were treated with LTFC. IOP was measured every 2 hours except from 01:00 and 05:00. Axial length, corneal curvature, and anterior chamber depth were obtained using the IOL master at baseline and 24 hours later. Adverse events were assessed by patient interview and by slit lamp examination. RESULTS: The largest difference in IOP between treated and untreated eyes 8 hours after instillation was 1.67 mmHg in the BTFC group (p < 0.001). The largest difference in IOP between treated and untreated eyes 10 hours after instillation was 1.93 mmHg in the LTFC group (p < 0.001). For anterior ocular parameters such as axial length, corneal curvature, anterior chamber depth at baseline and 24 hours after instillation, there were no significant differences between the baseline and 24-hour values in either the BTFC or LTFC group. The most frequently occurring adverse event was conjunctival hyperemia, which was found in 33.3% (n = 10) of the BTFC group and 25.0% (n = 7) of the LTFC group (p = 0.486). CONCLUSIONS: BTFC and LTFC provided a significant reduction in IOP from baseline without changing any anterior ocular parameters. Our results provide a reference for monocular trials to assess the effect of eye drops in a clinical condition.
Adult ; Aged ; Aged, 80 and over ; Amides/*administration & dosage ; Antihypertensive Agents/administration & dosage ; Circadian Rhythm/*physiology ; Cloprostenol/administration & dosage/*analogs & derivatives ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Glaucoma, Open-Angle/drug therapy/*physiopathology ; Healthy Volunteers ; Humans ; Intraocular Pressure/drug effects/*physiology ; Male ; Middle Aged ; Ophthalmic Solutions ; Prospective Studies ; Prostaglandins F, Synthetic/*administration & dosage ; Timolol/*administration & dosage ; Tonometry, Ocular ; Treatment Outcome