Previous article Table of Contents  Next article

ORIGINAL ARTICLE
Year : 2014  |  Volume : 8  |  Issue : 1  |  Page : 25-29

PONV in Ambulatory surgery: A comparison between Ramosetron and Ondansetron: a prospective, double-blinded, and randomized controlled study


1 Department of Anaesthesiology, MNC and H, Berhampur, West Bengal, India
2 C.M.S.D.H, Kolkata, West Bengal, India
3 NRS Medical College, Kolkata, West Bengal, India
4 Department of G and O, Burdwan Medical College, Burdwan, West Bengal, India
5 Department of Orthopedics, R.G. Kar Medical College, Kolkata, West Bengal, India

Correspondence Address:
Anjan Das
174, Gorakshabashi Road, Royal Plaza Apartment (4th floor, Flat No-1), Nagerbazar, Kolkata - 28, West Bengal
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1658-354X.125917

Rights and Permissions
Date of Web Publication1-Feb-2014
 

  Abstract 

Background: postoperative nausea and vomiting (PONV) frequently hampers implementation of ambulatory surgery in spite of so many antiemetic drugs and regimens. Aims: the study was carried out to compare the efficacy of Ramosetron and Ondansetron in preventing PONV after ambulatory surgery. Setting and Design: it was a prospective, double blinded, and randomized controlled study. Methods: 124 adult patients of either sex, aged 25-55, of ASA physical status I and II, scheduled for day care surgery, were randomly allocated into Group A [(n=62) receiving (IV) Ondansetron (4 mg)] and Group B [(n=62) receiving IV Ramosetron (0.3 mg)] prior to the induction of general anesthesia in a double-blind manner. Episodes of PONV were noted at 0.5, 1, 2, 4 h, 6 , 12, and 18 h postoperatively. Statistical Analysis and Results: statistically significant difference between Groups A and B (P <0.05) was found showing that Ramosetron was superior to Ondansetron as antiemetic both regarding frequency and severity. Conclusion: it was evident that preoperative prophylactic administration of single dose IV Ramosetron (0.3 mg) has better efficacy than single dose IV Ondansetron (4 mg) in reducing the episodes of PONV over 18 h postoperatively in patients undergoing day-care surgery under general anesthesia.

Keywords: Ambulatory (day care) surgery, American Society of Anaesthesiologists, Ondansetron, postoperative nausea and vomiting, Ramosetron, visual analogue score


How to cite this article:
Banerjee D, Das A, Majumdar S, Mandal RD, Dutta S, Mukherjee A, Chakraborty A, Chattopadhyay S. PONV in Ambulatory surgery: A comparison between Ramosetron and Ondansetron: a prospective, double-blinded, and randomized controlled study. Saudi J Anaesth 2014;8:25-9

How to cite this URL:
Banerjee D, Das A, Majumdar S, Mandal RD, Dutta S, Mukherjee A, Chakraborty A, Chattopadhyay S. PONV in Ambulatory surgery: A comparison between Ramosetron and Ondansetron: a prospective, double-blinded, and randomized controlled study. Saudi J Anaesth [serial online] 2014 [cited 2019 Nov 15];8:25-9. Available from: http://www.saudija.org/text.asp?2014/8/1/25/125917


  Introduction Top


Postoperative nausea and vomiting (PONV), one of the most common and distressing adverse events experienced by patients after an anesthesia and surgery [1],[2] may prolong recovery, delay patient discharge, and increase hospitalization costs. [1],[2] Prevention and treatment of PONV help in accelerating postoperative recovery and increase patient satisfaction. [3],[4] PONV is not uncommon after general surgery with incidence of 20-30%. [5],[6] PONV causes 0.17% unanticipated admission to the hospital following ambulatory surgery. [7]

Numerous studies have investigated the prevention and treatment of PONV for patients scheduled to undergo day-care surgeries by a variety of antiemetics including anticholinergics, [8],[9] antihistamines, [10] promethazine, [11] butyrophenones such as haloperidol [12] and droperidol. [13] However, these agents may cause undesirable adverse effects such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations, and extrapyramidal signs. [14] 5-HT3 antagonists prevent serotonin from binding to 5-HT3 receptors on the ends of the vagus nerve's afferent branches, which send signals directly to the vomiting center in the medulla oblongata and in the chemoreceptor trigger zone of the brain. [15] By preventing activation of these receptors, 5-HT3 antagonists interrupt one of the pathways leading to vomiting. [15] Ondansetron, the most commonly used prophylactic 5-HT3 antagonist, was found to be more effective than traditional antiemetics, such as droperidol and metoclopramide, in reducing the incidence of PONV. [16],[17],[18] Ramosetron, a new 5-HT3 receptor antagonist, has higher potency and prolonged activity than previously developed 5-HT3 antagonists as an antiemetic after chemotherapy, [19],[20] gynecological surgery, [21] laparoscopic surgery, [22] middle ear like day-care surgeries. [23]

The aim and objective of this study was to compare the antiemetic efficacy of these two drugs in the first 18 h postoperative period of a day-care surgery. The severity of PONV was recorded using VAS with choice options ranging from 0 (no nausea) to 10 (worst possible nausea).


  Methods Top


After obtaining permission from institutional ethics committee, written informed consent was taken. Total 124 adult patients were randomly allocated to two equal groups (n = 62 in each group) using computer generated random number list. Group A comprised patients who received single dose IV Ondansetron (4 mg) and group B comprised those who received single dose IV Ramosetron (0.3 mg).

Exclusion criteria

Patient refusal, any known allergy or contraindication to any of the two drugs, pregnancy, lactation and children, subjects who vomited or received antiemetics within 24 h before surgery, hepatic, renal or cardiopulmonary abnormality, alcoholism, diabetes, significant gastrointestinal disorders (for example peptic ulcer disease or gastro esophageal reflux disease) and motion sickness were excluded. As we were dealing with day-care surgery patients having no assistance in home and dwelling at more than 10 km from our institution were also excluded from our study.

In preoperative assessment, patients were enquired about heartburn, belching, and abdominal discomfort, h/o motion sickness, any antiemetic treatment received, h/o previous exposure to anesthesia and h/o PONV. The patients were enquired about any history of drug allergy, previous operations or prolonged drug treatment. General examination, systemic examinations, and assessment of the airway were done. Preoperative fasting of minimum 6 h was ensured before operation in all day-care cases. All patients received premedication of tablet diazepam 5 mg orally the night before surgery as per preanesthetic check up direction to allay anxiety, apprehension, and for sound sleep. The patients also received tablet ranitidine 150 mg in the previous night and in the morning of operation with sips of water.

The patients were preoxygenated with 100% oxygen for a period of 5 min. Injection fentanyl (2 μg/kg) and glycopyrrolate (0.01 mg/kg) were given intravenously 3 min before induction of anesthesia. All the patients were induced with IV injection of Thiopentone Sodium 2.5% (5 mg/kg) titrated till the loss of eyelash reflex. After that, atracurium (0.5 mg/kg) was given to facilitate laryngoscopy and intubation. Controlled ventilation was maintained with 33% oxygen in 67% nitrous oxide using Boyle's apparatus. Laryngoscopy, intubation, and cuff inflation were completed within 15 s in all cases. Muscle relaxation was maintained with intermittent intravenous atracurium (0.2 mg/kg) as and when required. Intraoperatively, the pulse rate, respiratory rate, arterial oxygen saturation, ECG, capnography, systolic, and diastolic pressure were monitored continuously. Ventilation was controlled manually and adjusted to maintain the End tidal CO 2 pressure (E T CO 2 ) between 35-45 mmHg. Laparoscopic surgeries were performed under video guidance and involved four punctures of the abdomen and abdomen insufflated with carbon dioxide through a veress needle to a maximum intra-abdominal pressure of 14 mmHg. At the completion of surgery, residual neuromuscular blockade was antagonized at TOF ratio more than 0.7 with neostigmine 0.05 mg/kg and atropine 0.02 mg/kg intravenously and patient was extubated in conscious condition. All the patients received tramadol 2 mg/kg IV 20 min before the end of surgery. The patients were then sent to the postoperative recovery unit. Postoperative analgesia was provided with injection diclofenac 50 mg intramuscularly. All patients received moist oxygen supplementation (3 l/min) for 2 h and standard minimum monitoring systems were used. All the patients were on intravenous drip and did not have any oral fluid during the study period of 12 h.

Throughout the 18 h of postoperative period, all the parameters were recorded on 0.5, 1, 2, 4, 6, 12, 18 h. All episodes of nausea, retching, vomiting, and rescue antiemetic provided were recorded by using score of Bellville and co-workers, [24] being the primary assessment parameter. Severity of PONV was observed by VAS scoring (0 represent 'no nausea' and 10 represents 'worst possible nausea') at same interval in the postoperative period. The time to first administration of rescue antiemetic and the total dose of rescue antiemetic were also recorded. If the patient experienced emetic episodes, retching or requested for treatment, rescue antiemetic was given with IV Metoclopramide (10 mg) slowly.

Statistical analysis

The raw data were entered into Microsoft excel spread sheet and analyzed by appropriate statistical software SPSS® statistical package version 18.0 (SPSS Inc., Chicago, IL, USA). Normally distributed numerical variables were compared between groups by independent sample t test. Chi square test, Officers exact test, and Fischer's exact test were used to compare categorical variables between groups. All analysis was two tailed and P < 0.05 was considered statistically significant.


  Results and Analysis Top


There were no statistically significant differences between the two groups in terms of demographic characteristics of the patients namely age, sex, and body weight, ASA status, duration of anesthesia and surgery [Table 1]. [Table 2] shows that types of surgical procedures were almost similar in both the groups and had no statistical significance. From [Table 3] it is clear that at 0.5 h and 18th hour episodes of PONV are not significantly different among the two groups but other readings show Ramosetron has controlled PONV more significantly than Ondansetron. Postoperative mean VAS scoring (in 18 h postoperative period) for the severity of PONV between the two study groups at same time intervals [Table 3] showed that at fourth and sixth postoperative hour period there was statistically significant difference between Groups A and B (P < 0.05), showing that severity of PONV is more in case of Ondansetron than Ramosetron.
Table 1: Comparison of demographic data between the two study groups

Click here to view
Table 2: Ambulatory surgical procedures for randomized patient groups

Click here to view
Table 3: Comparing the postoperative mean PONV episodes (in 12 h postoperative period) between the two study groups at succeeding time intervals

Click here to view


Again during the 18 h postoperative study period, the comparison of mean pulse rate, respiratory rate, systolic, and diastolic blood pressure showed that there was no clinically significant difference between the groups.


  Discussion Top


Day care surgery has proven over the years as the best method to reduce the burden on the health care resources as well as achievement of extreme patient satisfaction. [25] In developing countries like India, most of the patients avoid bearing expenses of prolonged hospital stay. At the same time the infrastructure in our country is not organized uniformly to smoothly deliver the day-care procedures. In the present day scenario, PONV still remains a big headache and nuisance for the surgeons and anesthesiologists as well as an irritating discomfort for the patients almost equal in intensity to pain. [26] The delayed convalescence, hospital readmission, delayed return to work of ambulatory patients; postoperative surgical morbidities such as pulmonary aspiration, wound dehiscence, bleeding from the wound, dehydration, electrolyte disturbances, and metabolic derangement due to excessive emetic episodes are few of the adverse consequences of the PONV. [27]

Various drugs regimens and antiemetic interventions have been tried from time-to-time for the prevention of PONV but with a variable success rate. This study was carried out mainly to see the comparative efficacy of the new and much promising long acting 5-HT3 antagonist Ramosetron against Ondansetron in day-care surgery.

The demographic profile, between two groups, which was statistically insignificant (P > 0.05) of our patients was quite similar with other research investigations and provided us the uniform platform to evenly compare the results obtained. A study conducted by Fujii et al. [28] in a total of 100 patients yielded similar results. The mean duration of anesthesia and surgery were almost comparable in both the groups with no significant statistical difference [Table 1].

From [Table 2] it is quite evident that types of surgical procedures were almost similar in both the groups and had no statistical significance.

The incidence of PONV is very less in both the groups [Table 3] within first half hour and is not statistically significant (P > 0.05) but with passage of time Ondansetron treated A group shows signs of PONV. In all the readings 1-12 h group A (Ondansetron) patients suffered a significantly high (P < 0.05) amount of PONV in comparison with group B (Ramosetron). Again at 18th hour PONV episodes become comparable among two groups. Our results in the first 18-hour period with Ramosetron are quite comparable with many other studies [21],[29],[30],[31] but comparison in a day-care setting has not been demonstrated by any literary evidence.

The postoperative mean VAS scoring (in 24 h postoperative period) between the two study groups at succeeding time intervals was compared that showed no significant difference between two groups at 0.5 th , 1 st , 2 nd , 12 th , 18 th h but at 4 th and 6 th h statistically significant difference found between Groups A and B (P < 0.05) [Table 4] suggesting that the severity of PONV was more after second hour in the case of Ondansetron than Ramosetron.
Table 4: Comparing the postoperative mean VAS Scoring (in 12 h postoperative period) for severity of PONV between the two study groups at succeeding time intervals

Click here to view


Analysis of the primary outcome variable (need for rescue antiemetic metoclopramide 10 mg slow IV; [Table 5]) indicated that 72.58% (45 of 62) of patients receiving Ondansetron required rescue antiemetic therapy, compared with 8.06% (5 of 62) of patients receiving Ramosetron that is undoubtedly statistically significant (P < 0.05). Although the Ramosetron group was superior, both groups had a good number of patients who experienced PONV even after day-care surgeries. There were some patients who had multiple episodes of nausea and vomiting especially in the first 18 h in both the groups but for comparison sake we included only the number of episodes and not the number of patients.
Table 5: Comparison of rescue antiemetic (Metoclopramide) use frequency between the study groups

Click here to view


Similar study was conducted by Choi et al. [30] in 94 female nonsmoker patients (aged 18-65 years), randomly allocated into either Ondansetron group (group O, n = 47) or the Ramosetron group (group R, n = 47) after lumbar spine surgery. They concluded that Ramosetron was superior to Ondansetron in terms of preventing vomiting and reducing the severity of nausea related to Fentanyl-based IV PCA. Hahm et al. [31] compared the prophylactic antiemetic efficacy of Ramosetron and Ondansetron in patients at high-risk for PONV after total knee replacement. The incidence of nausea between 2 and 24 h and the severity of nausea between 2 and 48 h were less in the Ramosetron group. Kim et al. [32] studied the comparison of Ramosetron with Ondansetron for the prevention of postoperative nausea and vomiting in patients undergoing gynecological surgery. The incidence of vomiting was lower in both the Ramosetron (17%) and the Ondansetron (20%) groups than in the placebo group (44%) during the first 24 h after surgery (P < 0.05). The VAS score for nausea was also lower in the Ramosetron and Ondansetron groups compared with the placebo group. They concluded that Ramosetron 0.3 mg IV was as effective as Ondansetron 8 mg IV in decreasing the incidence of PONV and reducing nausea severity in female patients during the first 24 h after gynecological surgery.

We conclude from the study that Ramosetron is a very effective, safe antiemetic in the prevention of PONV and preoperative prophylactic administration of single dose IV Ramosetron (0.3 mg) has better efficacy than single dose IV Ondansetron (4 mg) in reducing the incidence of PONV over first 18-h postoperative period, in patients undergoing ambulatory surgery under general anesthesia. A control group was not included in our study because we regarded it as unethical to withhold prophylaxis in these patients for PONV particularly when being posted for ambulatory surgery. Another limitation is that we compared Ramosetron and Ondansetron based on the known optimal doses without knowledge of their equipotent doses. The manufacturer's recommended doses of Ramosetron and Ondansetron are 0.3 and 4 mg intravenous, respectively, and were chosen for this study. However, a larger study with large sample size needs to be conducted to establish the author's point of view with solidarity. The study being conducted in a developing country, the authors could not measure some of the biochemical parameters of nausea and vomiting like C reactive protein, urea, aldehydes, and ketones. Another limitation of the study was the failure to obtain information after 18-h period.

 
  References Top

1.Watcha MF, White PF. Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology 1992;77:162-84.  Back to cited text no. 1
[PUBMED]    
2.Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, et al. Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 2003;97:62-71.  Back to cited text no. 2
[PUBMED]    
3.Stadler M, Bardiau F, Seidel L, Albert A, Boogaerts JG. Difference in risk factors for postoperative nausea and vomiting. Anesthesiology 2003;98:46-52.  Back to cited text no. 3
[PUBMED]    
4.Tramer MR. Strategies for postoperative nausea and vomiting. Best Pract Res Clin Anaesthesiol 2004;18:693-701.  Back to cited text no. 4
    
5.Philip BK. Patients' assessment of ambulatory anesthesia and surgery. J Clin Anesth 1992;4:355-8.  Back to cited text no. 5
[PUBMED]    
6.Gan TJ, Meyer TA, Apfel CC, Chung F, Davis PJ, Habib AS, et al. Society for ambulatory anesthesia guidelines for the management of postoperative nausea and vomiting. Anesth Analg 2007;105:1615-28.  Back to cited text no. 6
[PUBMED]    
7.Gold BS, Kitz DS, Lecky JH, Neuhaus JM. Unanticipated admission to the hospital following ambulatory surgery. JAMA 1989;262:3008-10  Back to cited text no. 7
    
8.Kranke P, Morin AM, Roewer N, Wulf H, Eberhart LH. The efficacy and safety of transdermal scopolamine for the prevention of postoperative nausea and vomiting: A quantitative systematic review. Anesth Analg 2002;95:133-43  Back to cited text no. 8
    
9.Bailey PL, Streisand JB, Pace NL, Bubbers SJ, East KA, Mulder S, et al. Transdermal scopolamine reduces nausea and vomiting after outpatient laparoscopy. Anesthesiology 2002;72:977-80.  Back to cited text no. 9
    
10.Kranke P, Morin AM, Roewer N, Eberhart LH. Dimenhydrinate for prophylaxis of postoperative nausea and vomiting: A meta-analysis of randomized controlled trials. Acta Anaesthesiol Scand 2002;46:238-44.  Back to cited text no. 10
[PUBMED]    
11.Parlow JL, Meikle AT, Vlymen Jvan, Avery N. Postdischarge nausea and vomiting after ambulatory laparoscopy is not reduced by promethazine prophylaxis. Can J Anaesth 1999;46:719-24.   Back to cited text no. 11
    
12.Büttner M, Walder B, von Elm E, Tramèr MR. Is low-dose haloperidol a useful antiemetic?: A meta-analysis of published and unpublished randomized trials. Anesthesiology 2004;101:1454-63.  Back to cited text no. 12
    
13.Domino KB, Anderson EA, Polissar NL, Posner KL. Comparative efficacy and safety of ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting: A meta-analysis. Anesth Analg 1999;88:1370-9.  Back to cited text no. 13
[PUBMED]    
14.Morgan GE, Mikhail MS, Murray MJ. Clinical Anesthesiology: Adjuncts to anesthesia. New York: McGraw-Hill; 2002. p. 242-52.  Back to cited text no. 14
    
15.Hesketh PJ, Gandara DR. Serotonin antagonists: A new class of antiemetic agents. J Natl Cancer Inst 1991;83:613-20.  Back to cited text no. 15
[PUBMED]    
16.Tramer MR, Moore RA, Reynolds DJ, McQuay HJ. A quantitative systematic review of ondansetron in the treatment established postoperative nausea and vomiting. Anesthesiology 1997;87:1277-89.  Back to cited text no. 16
    
17.Polati E, Verlato G, Finco G, Mosaner W, Grosso S, Gottin L, et al. Ondansetron verus metoclopramide in the treatment of postoperative nausea and vomiting. Anesth Analg 1997;85:395-9.  Back to cited text no. 17
[PUBMED]    
18.Paxton DL, Mckay CA, Mirakin KR. Prevention of nausea and vomiting after day case gynaecological laparoscopy. A comparison of ondansetron, droperidol, metoclopramide and placebo. Anesthesia 1995;50:403-6.  Back to cited text no. 18
    
19.Shi Y, He X, Yang S, Ai B, Zhang C, Huang D, et al. Ramosetron versus ondansetron in the prevention of chemotherapy-induced gastrointestinal side effects: A prospective randomized controlled study. Chemotherapy 2007;53:44-50.  Back to cited text no. 19
[PUBMED]    
20.Kang YK, Park YH, Ryoo BY, Bang YJ, Cho KS, Shin DB, et al. Ramosetron for the prevention of cisplatin-induced acute emesis: A prospective randomized comparison with granisetron. J Int Med Res 2002;30:220-9.  Back to cited text no. 20
[PUBMED]    
21.Fujii Y, Saitoh Y, Tanaka H, Toyooka H. Ramosetron for Preventing Postoperative Nausea and Vomiting in Women Undergoing Gynecological Surgery. Anesth Analg 2000;90:472-5.  Back to cited text no. 21
[PUBMED]    
22.Fujii Y, Uemura A, Tanaka H. Prophylaxis of nausea and vomiting after laparoscopic cholecystectomy with ramosetron: Randomised controlled trial. Eur J Surg 2002;168:583-6.   Back to cited text no. 22
[PUBMED]    
23.Fujii Y. Clinical Strategies for Preventing Postoperative Nausea and Vomiting After Middle Ear Surgery in Adult Patients. Curr Drug Safe 2008;3:230-9.  Back to cited text no. 23
    
24.Bellville JW, Bross ID, Howlans WS. A method for the clinical evaluation of antiemetic agents. Anaesthesioloy1959;20:753-60.   Back to cited text no. 24
    
25.Boothe P, Finegan BA. Changing the admission process for elective surgery: An economic analysis. Can J anaesth 1995;42:391-4.  Back to cited text no. 25
[PUBMED]    
26.Lee A, Gin T, Lau AS, Ng FF. A comparison of patients' and health care professionals' preferences for symptoms during immediate postoperative recovery and the management of postoperative nausea and vomiting. Anesth Analg 2005;100:87-93.  Back to cited text no. 26
[PUBMED]    
27.Gan TJ. Risk factors for postoperative nausea and vomiting. Anesth Analg 2006;102:1884-98.  Back to cited text no. 27
[PUBMED]    
28.Fujii Y, Tanaka H. Randomized, double-blind, placebo-controlled, dosed-finding study of the antiemetic effects and tolerability of ramosetron in adults undergoing middle ear surgery. Clin Ther 2003;25:3100-8.  Back to cited text no. 28
[PUBMED]    
29.Do SH, Ryu J. Ramosetron versus ondansetron for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Surg Endosc 2010;24:1798-99  Back to cited text no. 29
    
30.Choi YS, Shim JK, Yoon do H, Jeon DH, Lee JY, Kwak YL. Effect of ramosetron on patient-controlled analgesia related nausea and vomiting after spine surgery in highly susceptible patients: Comparison with Ondansetron. Spine (Phila Pa 1976) 2008;33:E602-6.  Back to cited text no. 30
    
31.Hahm TS, Ko JS, Choi SJ, Gwak MS. Comparison of the prophylactic anti-emetic efficacy of ramosetron, a newly developed 5-HT3 antagonist, and ondansetron in patients at high-risk for postoperative nausea and vomiting after total knee replacement. Anesthesia 2010;65:500-4.   Back to cited text no. 31
    
32.Kim Sl, Kim Sc, Baek YH, Ok SY, Kim SH. The comparision of Ramosetron with Ondansetron for prevention of postoperative nausea and vomiting in patients undergoing gynaecological surgery. Br J Anaesth 2009;103:549-53.  Back to cited text no. 32
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


This article has been cited by
1 Providing Value in Ambulatory Anesthesia in2015
Caroline D. Fosnot,Lee A. Fleisher,John Keogh
Anesthesiology Clinics. 2015; 33(4): 731
[Pubmed] | [DOI]



 

Top
 
Previous article    Next article
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  IN THIS Article
   Abstract
  Introduction
  Methods
  Results and Analysis
  Discussion
   References
   Article Tables

 Article Access Statistics
    Viewed1927    
    Printed30    
    Emailed0    
    PDF Downloaded179    
    Comments [Add]    
    Cited by others 1    

Recommend this journal