A comparative study of patient-controlled epidural fentanyl and single dose epidural morphine for post-caesarean analgesia

In a prospective, randomized, double-blinded study, 23 patients who had undergone Caesarean delivery under epidural anaesthesia were assessed to evaluate the effectiveness of patientcontrolled epidural analgesia (PCEA) with fentanyl compared with a single dose of epidural morphine for postoperative analgesia. Group A (n = 11) received epidural fentanyl 100 μg intraoperatively, then self-administered a maximum of two epidural fentanyl boluses 50 μg (10 μg · ml^?1) with a lockout period of five minutes for a maximum of two doses per hour. Group B (n = 11) received a single bolus of epidural morphine 3 mg (0.5 mg · ml^?1) intraoperatively and received the same instructions as Group A but had their PCA devices filled with 0.9% NaCl. Patients were assessed up to 24 hr for pain, satisfaction with pain relief, nausea and pruritus using visual analogue scales (VAS). The treatments for inadequate analgesia, nausea and pruritus as well as time to first independent ambulation were recorded. The ventilatory response to carbon dioxide challenge was measured at four and eight hours. Pain relief, satisfaction with pain relief, and the use of supplemental analgesics were similar in both groups. The mean 24 hr dose of epidural fentanyl used by group A patients was 680 μg. Pruritus was less common in Group A patients at the 8 and 24 hr observation periods (P < 0.0125). Both groups experienced the same degree of nausea and clinically unimportant respiratory depression. We conclude that PCEA with fentanyl provides analgesia equal to a single dose of epidural morphine and may be suitable for patients who have experienced considerable pruritus after epidural morphine adminstration.     

Brachial plexus block with a new local anaesthetic: 0.5 percent ropivacaine

A new local anaesthetic, ropivacaine hydrochloride, was used in a concentration of 0.5 per cent in 32 patients receiving a subclavian perivascular block for upper extremity surgery. One group (n = 15) received 0.5 per cent ropivacaine without epinephrine and a second group (n = 17) received 0.5 per cent ropivacaine with epinephrine in a concentration of 1:200,000. Anaesthesia was achieved in 87 per cent of the patients in both groups in all of the C5 through T1 brachial plexus dermatomes. Motor block was profound with 100 per cent of patients in both groups developing paresis at both the shoulder and hand and 100 per cent developing paralysis at the shoulder. There was a rapid initial onset of sensory block (a mean of less than four minutes for analgesia) with a prolonged duration (a mean of greater than 13 hr of analgesia). The addition of epinephrine did not significantly affect the quality or onset of sensory or motor block. The duration of sensory block was reduced by epinephrine at T1 for analgesia and at C7, C8, and T1 for anaesthesia. The duration of sensory block in the remaining brachial plexus dermatomes as well as the duration of motor block was not effected by epinephrine. There was no evidence of cardiovascular or central nervous system toxicity in either group with a mean dose of 2.5-2.6 mg.kg-1 ropivacaine.     

Timing of caudal block placement in relation to surgery does not affect duration of postoperative analgesia in paediatric ambulatory patients

The purpose of this study was to determine if the timing of caudal block placement in relation to surgery affected either the duration of postoperative pain relief or the discharge time in children undergoing brief ambulatory surgical procedures. Forty ASA physical status I or II children ages 18 mo to 11 yr were randomly assigned to one of two groups. Group I patients received a caudal block with 0.5 ml · kg^?1 of bupivacaine 0.25 per cent following the induction of anaesthesia but before the onset of surgery. Group 2 patients received a similar block at the completion of surgery but before emergence from general anaesthesia. An experienced observer, who was not aware of the timing of block placement, observed all patients from arrival to the post-anaesthetic recovery room until discharge from the ambulatory surgery unit. Pain was assessed at five-minute intervals using an Objective Pain Scale. No statistically significant differences were noted between Group I and Group 2 patients with regard to their postoperative pain/discomfort scores, the need for postoperative narcotic analgesia, or the time required for either group to meet standard discharge criteria. It is concluded that the duration of postoperative analgesia is not impaired by placing the caudal block prior to the start of a brief surgical procedure.     

Prophylactic oral ephedrine reduces the incidence of hypotension after subarachnoid block

The purpose of this study was to demonstrate the efficacy of oral ephedrine in preventing hypotension following subarachnoid block. Two hundred women, ASA physical status I or II, undergoing lower abdominal surgery were randomly divided into two groups (n = 100 each). All patients were given routine oral premedication consisting of diazepam 10 mg and ranitidine 150 mg at bed time and at 90 min before surgery. In addition, Group I patients received ephedrine 30 mg, orally, 30 min before subarachnoid block was administered. Group II received only routine premedication. After starting an iv line and preloading with 10 ml · kg^?1 crystalloid, patients were given 0.5% heavy bupivacaine 3.2 to 3.6 ml, depending on body weight, intrathecally. Patients with decreases in blood pressure of 20% were given ephedrine iv, in increments, in addition to crystalloids. Despite a similar level of block (T₃–T₄) and iv fluids, the total dose of ephedrine supplement in Group I was 4.3 ± 4.8 mg compared with 11.6 ± 9.4 mg in Group II (P < 0.01). Also, 55 patients in Group I required intraoperative inotrope supplement compared with 83 in Group II (P < 0.01). We conclude that oral ephedrine premedication is a simple and effective way of reducing the incidence of hypotension in patients undergoing lower abdominal surgery under subarachnoid block.     

Brachial plexus block with bupivacaine: effects of added alpha-adrenergic agonists: comparison between clonidine and epinephrine

The effects of clonidine and epinephrine, administered into the brachial plexus sheath, were evaluated in 60 patients who underwent surgery of the upper limb. All patients received 40 to 50 ml of 0.25% bupivacaine, injected into the brachial plexus sheath, using the supraclavicular technique. The patients were randomly allocated to two groups so that 30 patients received 150 micrograms clonidine hydrochloride (Group I), and 30 received 200 micrograms epinephrine (Group II). The quality and the duration of analgesia were assessed as well as the possible side-effects. The block produced with the addition of clonidine was longer (994.2 +/- 34.2 vs 728.3 +/- 35.8 min) and superior to that with epinephrine (P less than 0.001). No major side-effects were recorded. We conclude that the injection of clonidine into the brachial plexus sheath is an attractive alternative to epinephrine to prolong the duration of analgesia following upper limb surgery under conduction anaesthesia.     

Lateral popliteal sciatic nerve block compared with subcutaneous infiltration for analgesia following foot surgery

A new lateral approach to blocking the sciatic nerve in the popliteal fossa is described. In a prospective study, 40 patients scheduled for foot surgery involving osteotomies were allocated randomly into one of two groups following induction of general anaesthesia: group PS (n = 21) received a lateral popliteal sciatic nerve block and group SC (n = 19) received subcutaneous infiltration of the wound. Both groups received 20 ml bupivacaine 0.5% plain. The lateral approach to the popliteal sciatic nerve was found to be an effective, quick, and easy to perform, block. Postoperative analgesia in groups PS lasted a median of 18.0 hr and in group SC lasted 6.3 hr (P < 0.05). The lateral popliteal sciatic nerve block provided effective analgesia following foot surgery and had a high level of patient satisfaction.     

Combined spinal epidural block versus spinal and epidural block for orthopaedic surgery

In a controlled study a single segment combined spinal epidural (CSE) block was compared with spinal or epidural block for major orthopaedic surgery. Seventy-five patients, age 52–86 yr, were randomly assigned to receive one of the three blocks. Bupivacaine 0.5% was used for surgical analgesia. The postoperative pain relief after 4.0 mg epidural morphine was compared with the analgesic effect of 0.2 or 0.4 mg morphine administered intrathecally. With the spinal technique good or excellent surgical analgesia and muscle relaxation were achieved rapidly (11.8 ± 1.1 min). The time taken to provide an equally effective and reliable block with the CSE technique was no longer (14.9 ± 2.2 min). For epidural block with the catheter technique more time was required (35.9 ± 3.9 min) to provide acceptable surgical conditions (P < 0.05). Perioperative sedatives and concomitant analgesics were required more frequently and in larger doses by the patients undergoing surgery with epidural block (P < 0.05) than with CSE or spinal block. Our study demonstrated that the analgesia after surgery provided by 0.2 and 0.4 mg morphine administered intrathecally was comparable to that provided by 4.0 mg of epidural morphine. It is concluded that the analgesia and surgical conditions provided by the spinal and CSE blocks were similar and were superior to those provided by an epidural block.     

Comparison of plain with pH-adjusted bupivacaine with hyaluronidase for peribulbar block

Fifty patients scheduled for cataract surgery under peribulbar block were randomised to receive either plain (pH 5.4) or pH-adjusted (pH 6.8 range 6.7-6.9) 0.75% bupivacaine. Hyaluronidase was added to both solutions prior to peribulbar block. The time of onset of akinesia of the globe and the need for supplementary injections were recorded by an independent observer. Patients who returned for surgery to the second eye received the alternative local anaesthetic solution for the second peribulbar block. The relative efficacy of the different anaesthetic solutions was compared in patients who underwent unilateral surgery (Group A, n = 50). In 12 patients (Group B) who underwent bilateral surgery, direct comparisons between eyes in the same patient were possible. In both groups of patients, eyes receiving peribulbar block with the pH-adjusted solution showed a shorter time to partial akinesia of the globe (P less than 0.05). However, there was no difference between the solutions in the time to complete akinesia of the globe, but the number of supplementary injections required for an effective block with the pH-adjusted solution was increased. Onset time to akinesia of the lateral and superior rectus muscles was shortened in patients receiving the pH-adjusted solution but there were minimal effects on the medial and inferior recti.     

Continuous suprascapular nerve block for analgesia of scapular fracture

Fracture of the scapular is uncommon but painful. A case is described in which a comminuted scapular fracture was treated with a continuous suprascapular nerve block. With the patient lying supine an epidural needle was directed towards the scapular notch via a superior approach and an epidural catheter was placed when the notch was believed to have been identified. Repeat injections of 10 ml bupivacaine 0.25 per cent with 1/200,000 epinephrine provided analgesia within minutes and a duration of 8-10 hr. Injection of 10 ml radio-opaque dye demonstrated the catheter to be lateral to the scapular notch. However, dye dispersed throughout the supraspinous fossa including the scapular notch thus blocking the suprascapular nerve. This case demonstrates that continuous suprascapular nerve block can be performed for five days and that location of the scapular notch is less important than previously thought.     

Transsartorial approach for saphenous nerve block

Blockade of conduction in the saphenous nerve is important in providing surgical anaesthesia in the lower leg. Unfortunately, previously described techniques have lacked clinical effectiveness in practice. We developed a transsartorial approach for conduction block of the saphenous nerve. We first confirmed its potential clinical utility in 12 cadaveric specimens by demonstrating that the saphenous nerve was consistently stained by injections of methylene blue. Subsequently, we compared the relative rates of successful saphenous nerve block and the extent of conduction block provided by three techniques: (1) transsartorial saphenous nerve block (TSSNB), (2) above knee femoral paracondylar field block (FPFB), and (3) below knee field block (BKFB) of the saphenous nerve in 20 ASA I volunteers. The transsartorial saphenous nerve block proved to be highly successful (80% success rate) and was superior to the other two approaches in providing cutaneous analgesia to pinprick in the saphenous nerve distribution (P < 0.05). The success rates of the BKFB and FPFB were 65% and 40% respectively. A successful block with the transsartorial approach provided complete anaesthesia of the medial malleolus in 94% of subjects whilst the BKFB and FPFB provided complete anaesthesia of the medial malleolus in less than 40% of the successful blocks. We recommend the transsartorial approach for more effective block of the saphenous nerve.     

Analgesic and pulmonary effects of continuous intercostal nerve block following thoracotomy

This study examined the beneficial effects and potential systemic toxicity from continuous intercostal nerve block by repeated bolus injections of bupivacaine. In this double-blind, randomized study, 20 post-thoracotomy patients were assigned to receive four doses of either: 20 ml 0.5% bupivacaine with epinephrine 5 micrograms.ml-1 (bupivacaine group, n = 10), or 20 ml preservative-free saline (placebo group, n = 10) through two indwelling intercostal catheters every six hours. Patients receiving intercostal bupivacaine injections had greater decreases in visual analogue pain scores (VAS) (P less than 0.05) and lower 24 hr morphine requirements, 16.6 +/- 4.6 mg vs 35.8 +/- 7.2 mg, than patients in the placebo group (P less than 0.05). Higher post-injection values of forced expiratory volume in one second, forced vital capacity and peaked expiratory flow rate were also observed in the bupivacaine group (P less than 0.01). Repeated intercostal bupivacaine administration did lead to systemic accumulation, but the peak bupivacaine level after 400 mg was low at 1.2 +/- 0.2 microgram.ml-1. Thus, the technique of continuous intercostal nerve block described in this study is an effective treatment for the control of post-thoracotomy pain.     

Posterior approach to the lumbar plexus combined with a sciatic nerve block using lidocaine

A combination of lumbar plexus block, by a posterior technique, and sciatic nerve block can be a useful technique for outpatient anaesthesia. The purpose of this study was to examine the clinical characteristics of these blocks using lidocaine and to measure the serum lidocaine concentrations. Forty-five patients, undergoing lower extremity surgery, were studied. Sciatic nerve and lumbar plexus blocks were made with lidocaine, 680 mg with adrenaline 0.3 mg. For each patient the following data were collected: weight, age, sex, site of surgery, time to perform each block, needle depth, speed of onset of the sensory and motor blocks in the territories of the sciatic, femoral, obturator and lateral cutaneous (sensory) nerves and postoperative analgesic requirements. Lidocaine serum concentrations were measured in ten of these patients at 0, 2, 5, 10, 30, 60, 90 and 120 min after the second block. Analgesia was complete in 88% (40/45) of the patients. The remaining five patients needed analgesics (fentanyl 150 μg or less). Despite the high dose of lidocaine, the serum concentrations were within safe limits (mean ± SD) (C_MAX = 3.66 ± 2.21 μg · ml^?1). Only one patient had a serum concentration > 5 μg · ml^?1 (C_MAX = 9.54 μg · ml^?1). This was associated with a contra-lateral extension of the block. We conclude that this combination of blocks is a valuable alternative for unilateral lower extremity anaesthesia. However, clinicians must be aware of the implications of a contra-lateral extension of the block.     

Clinical and pharmacokinetic aspects of the combination of meperidine and prilocaine for spinal anaesthesia

The aim of this study was to determine whether the addition of a small dose of prilocaine could augment the spinal block induced by meperidine and affect intrathecal meperidine pharmacokinetic behaviour. Spinal anaesthesia was performed in 60 men scheduled for endoscopic resection of a prostatic adenoma or bladder tumour under spinal anaesthesia. They were allocated randomly to receive either 1 mg.kg-1 meperidine (Group 1, n = 30), or 1 mg.kg-1 meperidine plus 0.5 mg.kg-1 prilocaine (Group 2, n = 30). Blood samples were collected prior to and for 24 hr after spinal injection in 24 patients (12 in each group). Plasma meperidine levels were assayed by gas chromatography. Complete motor block was achieved in all Group 2 patients, but was incomplete in seven of Group 1 (P less than 0.05). The onset of both motor and sensory blocks was shorter (P less than 0.01) in Group 2 and the duration was longer (P less than 0.05). Coadministration of prilocaine modifies meperidine pharmacokinetic behaviour. The area under curve was 48% greater (P less than 0.01) and Cmax was higher in Group 2 than in Group 1, 145.8 +/- 42.2 vs 107 +/- 20.5 ng.ml-1 (P less than 0.001). No evidence of respiratory depression was noted in any of the patients. Despite the increase in plasma meperidine concentrations, no side effects were observed. The plasma concentrations remained at one third to one sixth the levels reported to induce a respiratory depression. It is concluded that the addition of prilocaine to meperidine improves motor and sensory block during surgery and alters meperidine kinetics without producing major side effects.     

Preoperative naproxen sodium reduces postoperative pain following arthroscopic knee surgery

This study was undertaken to assess the efficacy of a single preoperative dose of naproxen sodium in reducing postoperative pain and length of day surgery stay in patients undergoing arthroscopic knee surgery. A randomized, double-blind clinical trial was carried out on 66 ASA I and ASA II patients scheduled for arthroscopic knee surgery. The treatment group (n = 26) received two capsules containing 275 mg of naproxen sodium each, and the control group (n = 40) received placebo. Preoperative and postoperative visual analogue pain scores, postoperative analgesic requirements in hospital as well as 24 hr after discharge, and length of day surgery stay were studied. There was a decrease in postoperative pain, both in hospital (naproxen 0.7 ±1.2 vs placebo 2.2 ±2.3) and at 24 hr after discharge (naproxen 0.8 ±1.9 vs placebo 3.8 ±3.2) (P = 0.0001). There was no difference in the need for in-hospital postoperative analgesics or in the time to discharge. However, there was a difference in the use of analgesics after discharge (naproxen group 30.4% vs placebo group 71.4%) (P < 0.01). The results of this study suggest that a single preoperative dose of 550 mg naproxen sodium is effective in reducing postoperative pain in arthroscopic knee surgery, both in the immediate postoperative period and for up to 24 hr after the completion of surgery.     

Repeat epidural analgesia and unilateral block

The use of epidural analgesia has become so widespread in recent years that many women are now requesting repeat epidural analgesia for their second or subsequent labour. This study examines the incidence of problems at insertion and of inadequate block in 71 multiparae having second epidurals compared with 150 primiparae having their first epidural. Unilateral block occurred in 6.66% of primiparae and 18.3% of multiparae (P) <0.02). There was no association between difficulty of insertion of catheter, blood in needle/catheter or paraesthesia and unilateral blockade. Epidurals were inserted at a greater dilatation (P <0.05 and there was a shorter time to delivery (P < 0.01) in the multiparous group. We conclude that unilateral block is thus more common in women receiving repeat epidurals.     

Intrathecal meperidine for elective Caesarean section: a comparison with lidocaine

The purpose of this study was to determine the efficacy of intrathecal meperidine in patients undergoing Caesarean section, and also to compare meperidine with heavy lidocaine. Fifty fall-term pregnant women, ASA physical status I or II, presenting for elective Caesarean section under spinal anaesthesia were randomly divided into two groups with 25 in each, to receive either intrathecal meperidine or lidocaine. All patients received premedication with oral ranitidine, 150 mg, the night before surgery, and again two hours before surgery. Patients in the meperidine group were also given metoclopramide iv 10 mg one hour before surgery. After iv 20 ml·kg^?1 Ringer’s lactate, patients were given either 5% meperidine 1 mg · kg^?1 or 5% heavy lidocaine 1.2 to 1.4 ml intrathecally. The sensory and motor blockades in all except two patients in each group who required sedation at the time of skin incision were adequate for surgery. None of the mothers suffered from any major side effects. The incidence of hypotension was higher in the lidocaine group than in meperidine group (P < 0.05). Pruritus and drowsiness were more common in meperidine group than in lidocaine group (P < 0.01). All the newborns in both groups cried immediately after birth and had an Apgar scope > 7. The mean duration of postoperative analgesia was six hours in the meperidine group and one hour in the lidocaine group (P < 0.01). Postoperative analgesia requirement was less in the meperidine than in the lidocaine group (P < 0.01). It is concluded that intrathecal 5% meperidine in a dose of 1 mg·kg^?1 is superior to 5% heavy lidocaine because of the prolonged postoperative analgesia. The commercial 5% solution of meperidine can be used, without addition, for this purpose.     

The benefit of the Hemonetics® cell saver apparatus during cardiac surgery

This retrospective chart review of 155 patients having coronary artery bypass graft surgery (CABG) over a two-month period determined whether the use of a cell saver apparatus (CSA) (1) reduced or increased the requirements for homologous blood; (2) increased the incidence of post-surgical bleeding; (3) was cost-effective. Two groups of patients were identified. Group 1 (n = 99) received both CSA processed red blood cells and homologous blood components. Requirement for homologous blood products was reduced in the first 24 hr after surgery (0.5 +/- 1.0 vs 1.3 +/- 1.8 units; P less than 0.05) when compared with Group 2 (n = 56) in whom only homologous blood products were utilized. More patients in Group 1 had no transfusion requirements (45 vs 8; P less than 0.05) and there was no increased risk of major haemorrhage. When the capital costs are included, utilization of the CSA was not cost-effective. We conclude that utilisation of a CSA was safe, with no increased risk of bleeding, reduced requirements for homologous blood transfusions, but added to the cost of the procedure.     

Epidural opioid analgesia after Caesarean section: a comparison of patient-controlled analgesia with meperidine and single bolus injection of morphine

The quality of analgesia, patient satisfaction and incidence of side effects following a single bolus of epidural morphine were compared with patient-controlled epidural analgesia (PCEA) with meperidine during the first 24 hr after elective Caesarean section. Seventy-five women were randomly assigned to three equal groups. Group 1 received 30 mg epidural meperidine after delivery and PCEA with meperidine; Group 2 received 3 mg epidural morphine after delivery and PCEA with saline in a double-blind fashion. Group 3 received 3 mg epidural morphine after delivery without saline PCEA. Visual analogue pain scores (VAS) were higher with PCEA meperidine from 8–16 hr postoperatively (P < 0.05) than in both epidural morphine groups. Two patients in Group 1 and one in Group 3 required supplemental parenteral analgesia. The incidence of nausea was 16% in Group 1, compared with 52% in Group 2 and 56% in Group 3 (P < 0.01). Pruritus occurred in 24% of Group 1 patients, 84% of patients in Group 2 and 68% of patients in Group 3 (P< 0.001). Forty-six percent of patients in Group 1 were very satisfied with pain management, compared with 77% in Group 2 and 79% in Group 3. Nurse workload was higher in the PCEA study groups than in Group 3 (P< 0.05). A single bolus of epidural morphine provides superior analgesia and satisfaction at low cost, but with a higher incidence of nausea and pruritus than PCEA with meperidine.     

Postoperative neuromuscular block following atracurium or alcuronium in children

Postoperative neuromuscular block (NMB) was evaluated in 60 children who received randomly either atracurium or alcuronium to induce and maintain an 85-95 per cent NMB during balanced anaesthesia. The EMG-monitor was turned away from the anaesthetist 10-15 min before the end of surgery. The average NMB was comparable between the groups at the time of reversal with neostigmine 50 micrograms.kg-1 (84 +/- 9 per cent, mean +/- SD) as were the NMB and the train-of-four ratio when the tracheas were extubated on a clinical basis (32 +/- 20 per cent and 50 +/- 18 per cent, respectively). Patients who had been paralyzed with atracurium arrived at the recovery room earlier and on arrival had greater train-of-four ratios than the patients paralyzed with alcuronium (P less than 0.01). Time to a train-of-four ratio of greater than 90 per cent was significantly shorter in the atracurium group (10 +/- 5 min vs 26 +/- 15 min, P less than 0.001). Thus, an intermediate-acting muscle relaxant offers a safer recovery profile of the NMB than a long-acting muscle relaxant in paediatric patients.     

A singleiv dose of ondansetron 8 mg prior to induction of anaesthesia reduces postoperative nausea and vomiting in gynaecological patients

The effect of a single intravenous dose of ondansetron in preventing postoperative nausea and emesis (retching and vomiting) (PONV) was investigated in a randomized, double-blind, placebo-controlled, multicentre, international study. Women of ASA class I–III, requiring gynaecological laparotomy, vaginal hysterectomy, or major vaginal surgery were selected for study. Two hundred and thirty-five received placebo, 231 received 1 mg ondansetron, 228 received 8 mg ondansetron and 229 received 16 mg ondansetron, as an infusion over five minutes before the induction of anaesthesia. A standardized balanced anaesthetic technique was employed. This consisted of premedication with either diazepam or temazepam, thiopentone induction, maintenance with nitrous oxide in oxygen supplemented with enflurane or isoflurane, intraoperative analgesia with fentanyl, neuromuscular blockade with any choice of agent and reversal with neostigmine and atropine. Postoperative analgesia was achieved with morphine, and prochlorperazine or metoclopramide were given if a rescue antiemetic was required. A greater percentage of patients in the 8 mg and 16 mg ondansetron groups experienced no postoperative emesis (44% and 39% respectively) than in the placebo and 1 mg ondansetron groups (29% and 28% respectively) for the first 24 hr postoperative period (8 mg vs placebo and 1 mg: P ≤ 0.001; 16 mg vs placebo: P < 0.05; 16 mg vs 1 mg: P < 0.05). Similarly, the percentage of patients who did not experience postoperative nausea were 20%, 26%, 31% and 28% for the placebo, 1 mg, 8 mg and 16 mg ondansetron treatment groups, respectively (8 mg and 16 mg vs placebo P < 0.05). Overall, the incidences of adverse events in the ondansetron and placebo groups were similar. It is concluded that intravenous ondansetron, at doses of 8 mg and 16 mg, is both well tolerated and effective in preventing postoperative nausea and emesis, and no greater benefit was observed with the 16 mg dose in comparison with the 8 mg dose.