Journal of Clinical Anesthesia (2006) 18, 114 – 117

Original contribution

A novel mixture of propofol, alfentanil, and lidocaine for

regional block with monitored anesthesia care in
ophthalmic surgery
Zhuang T. Fang MD, MSPH (Assistant Professor of Clinical Anesthesiology)*,
Mary A. Keyes MD (Professor of Clinical Anesthesiology)

Department of Anesthesiology, Center for Health Sciences, David Geffen School of Medicine at UCLA, Box 951778,
Los Angeles, CA 90095-1778, USA

Received 18 May 2004; accepted 11 August 2005

Keywords: Abstract
Alfentanil; Study Objective: The purpose of this study is to determine the efficacy and safety of sedation/analgesia
Propofol; using a mixture of propofol, alfentanil, and lidocaine.
Sedation; Design: A retrospective case review was undertaken.
Analgesia; Setting: This study took place at a university medical center.
Monitored anesthesia care Patients: Eighty-nine American Society of Anesthesiologists physical status 1, 2, and 3 adult patients
undergoing ophthalmic surgery with regional block and monitored anesthesia care were studied.
Intervention: Six milliliters of propofol, 2 mL of alfentanil, and 2 mL of 2% lidocaine (6-2-2 mixture)
were freshly mixed. The bolus dose was determined based on the patients’ age: 5 lg/kg of alfentanil
(and 0.3 mg/kg of propofol) for patients older than 75 years; the dose increased 1 lg/kg per 10-year
decrease in age; and up to 9 lg/kg of alfentanil (0.54 mg/kg of propofol) for patients younger than
45 years. Regional block was performed at 1 minute after bolus completion. Blood pressure (BP), Sao2,
electrocardiogram, capnography, clinical signs of sedation, responses to block, need for airway support,
nausea and vomiting (N/V), pain due to propofol infusion, recall, and patient and surgeon satisfaction
were recorded.
Measurements and Main results: Seventy-eight percent of patients achieved analgesia and sedation
without adverse response to the block. Twelve percent achieved good analgesia and sedation with only
eyebrow movement upon needle insertion. Twenty-seven percent had respiratory depression but were
able to follow commands and maintain adequate ventilation. Two percent had brief apnea alleviated by
chin lift or jaw thrust. None had pain because of propofol infusion or N/V. Before sedation, average
systolic BP was significantly increased ( P b 0.0001) compared with baseline. After sedation and block,
systolic BP decreased 6% from baseline ( P b 0.005).
Conclusion: Adjusted for age and weight, the dose of the 6-2-2 mixture met the sedation requirements
for most patients. With a low incidence of need for airway support, no pain during infusion, and no N/V,

4 Corresponding author. Tel.: +1 310 825 6761; fax: +1 310 794 2141.
E-mail address: zfang@mednet.ucla.edu (Z.T. Fang).

0952-8180/$ – see front matter D 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.jclinane.2005.08.007
MAC in ophthalmic surgery
this novel mixture of propofol, alfentanil, and lidocaine provided adequate analgesia and sedation as
well as hemodynamic stability for ophthalmic surgery under regional block.
D 2006 Elsevier Inc. All rights reserved.
1. Introduction
Most ophthalmic surgeries are currently performed with
regional nerve block. Although brief, it is a painful and
stressful stimulus associated with adverse hemodynamic
changes, such as hypertension and tachycardia. There are
also elevated levels of catecholamines, cortisol, prolactin,
homocysteine, leukocytosis, and insulin resistance, all of
which may increase perioperative morbidity and mortality
[1-5]. Clinical studies of monitored anesthesia care using
sedation and analgesia to alleviate stress and pain have
shown that propofol and/or midazolam, in combination with
short-acting opioids (alfentanil, sulfentanil, fentanyl, and
remifentanil), and/or ketamine are superior to the single use
of any one drug [6-9]. The mixture of propofol and
alfentanil has been shown to be effective in providing
sedation and analgesia for ophthalmic surgery and is used
routinely in our institution [10]. We have recently modified
the protocol to reduce the volume of propofol from 8 to
6 mL, include the addition of 2 mL of 2% lidocaine, and
maintain 2 mL of alfentanil (1000 lg) as a 6-2-2 mL
mixture. The addition of lidocaine diminishes or eliminates
the pain on injection of propofol, and with the 2 mL of
alfentanil, dilutes the propofol to 6 mg/mL. This dilution
optimizes the dose of alfentanil for maximum analgesia
without causing oversedation by propofol.
2. Materials and methods
After approval by the institutional review board, we
retrospectively reviewed 89 charts of patients who underwent
ophthalmic procedures under retrobulbar block or regional
field block injection of local anesthetics while being sedated
with the modified mixture of propofol, alfentanil, and
lidocaine. Patients who were on chronic pain medications
or benzodiazepines and those with hearing disability,
psychiatric disease, or language barrier were excluded.
Propofol 6 mL (10 mg/mL, AstraZeneca, Wilmington, DE,
USA), alfentanil 2 mL (0.5 mg/mL, Janssen-Ortho, Inc.,
Toronto, ON, Canada), and 2% lidocaine 2 mL (AstraZeneca
LP, 20 mg/mL) were freshly mixed in a 10-mL syringe (6-2-2
mixture). The final concentration was propofol 6 mg/mL,
alfentanil 100 lg/mL, which is used as the concentration for
the setup of the infusion pump, and lidocaine 4 mg/mL. A
bolus dose of the 6-2-2 mixture was determined based on the
patients’ age and weight (Table 1).
No premedication or intravenous lidocaine were given
before the administration of the mixture. The bolus dose was
delivered by an infusion pump (model AS50, Baxter,
Healthcare Corp., Round Lake, IL, USA) and followed by
115
a continuous infusion of alfentanil (0.75 lg/kg per minute),
propofol (45 lg/kg per minute), and lidocaine (30 lg/kg per
minute) until block completion. The duration time for bolus
administration was recorded. The regional block was per-
formed 1 minute after bolus administration was completed.
Modifications to the drug dosing were done if the body
mass index (BMI) exceeded 26. Weight for dosing was
calculated as ideal body weight (IBW) plus 30% of the
difference between the patient’s weight and IBW based on
the pharmacokinetics of propofol in obese patients [11] and
the addition of alfentanil in the mixture.
Oxygen was provided by nasal canula. Blood pressure
(BP), pulse oximetry, electrocardiography, capnography,
apnea, need for airway support, nausea and vomiting (N/
V), and recall of regional block were recorded. Modified from
the Observer’s Assessment of Alertness/Sedation [12], 4
clinical signs of sedation (spontaneous eye closure, sluggish
speech, decreased respiratory rate, and loss of consciousness)
and 3 responses to the nerve block (eyebrow movement, head
movement, and complaint of pain) were also recorded.
Surgeon and patient satisfaction were scored (1-10) by
standardized questions after the block. Exact v 2 and Student
t tests or corresponding Wilcoxon rank sum test was used
for statistical analysis. P b 0.05 was considered significant.
3. Results
The charts of 89 American Society of Anesthesiologists
physical status 1, 2, and 3 patients (45 women and 44 men),
aged 30 to 85 years, were reviewed. The surgeries in-
cluded trabeculectomy, Ahmed valve placement for glau-
coma, vitrectomy for retinal detachment or diabetic
retinopathy, corneal transplant, oculoplastic surgery, and
cataract extraction. The average time for the delivery of the
Table 1 Bolus dose of 6-2-2 mixture
Age (y) Bolus dose
N74 5 lg/kg alfentanil, 0.30 mg/kg
propofol + 0.20 mg/kg lidocaine
65-74 6 lg/kg alfentanil, 0.36 mg/kg
propofol + 0.24 mg/kg lidocaine
55-64 7 lg/kg alfentanil, 0.42 mg/kg
propofol + 0.28 mg/kg lidocaine
45-54 8 lg/kg alfentanil, 0.48 mg/kg
propofol + 0.32 mg/kg lidocaine
b45 9 lg/kg alfentanil, 0.54 mg/kg
propofol + 0.36 mg/kg lidocaine
A6-2-2 mixture = 6 mL of propofol, 2 mL of alfentanil, 2 mL of
2% lidocaine.
116 Z.T. Fang, M.A. Keyes

Table 2 Patient response to the sedation of 6-2-2 mixture during regional blocks
No. of Response/ No ebm only RD-FC Apnea, need SBP SBP N/V Nonstressful
patients No response hm/ebm/cop for airway (pre-bl) (post-bl) recall
sec/ss/drr support (mmHg) (mmHg)
89 71 (80%) 69 (78%) 11 (12%) 24 (27%) 2 (2%) 14 F 23 8 F 22 0 45 (50%)
P b 0.0001 P b 0.005
sec indicates spontaneous eye closure; ss, sluggish speech; drr, decreased respiratory rate; hm, head movement; ebm, eyebrow movement; cop, complaint of
pain; RD-FC, respiratory depression but able to follow command; SBP (pre-bl), SBP difference between baseline and that before sedation; SBP (post-bl),
difference between baseline and that after sedation; Nonstressful recall=neither unpleasant nor painful for the patient.

bolus of the 6-2-2 mixture was 2 to 3 minutes, depending on taining the airway, oxygenation, and hemodynamic stability.
the patients’ age and weight (0.29 F 0.04 seconds per Although there is variability among patients with regard to
microgram of bolus of alfentanil). Overall, 80% of the drug and sedation requirements, in clinical practice, it is
patients showed 3 signs of adequate sedation and opioid necessary to find a range of drug dosages to fit most patients
effect (spontaneous eye closure, sluggish speech, and with minimal side effects, especially in a high-volume
decreased respiratory rate) without loss of consciousness. ambulatory setting. In our study, the technique of using the
Four (4.5%) of 89 patients had brief loss of consciousness. 6-2-2 mixture met the needs for most patients with adequate
Seventy-eight percent tolerated the regional block without analgesia and sedation, yet minimum airway and hemody-
eyebrow movement, head movement, or complaint of namic adverse effects. With the 6-2-2 mixture, the patients
pain. Twelve percent of patients felt the sensation or mild
pain from the needle insertion leading to eyebrow move-
ment, but tolerated the injection without head move- Table 3 Demographic profile of normal weight vs over-
ment (Table 2). There were no complaints of pain from the weight/obese patients and response to the 6-2-2 sedation and
mixture infusion or N/V. Twenty-seven percent of patients regional block
showed respiratory depression (respiratory rate b8), but Nonobese Obese P
were able to follow commands and maintained adequate No. 40 49 NS
ventilation. Only 2% of the patients had brief apnea (less Female 49% 53% NS
than a minute) with oxygen desaturation (b90%), which Age 67 F 14 65 F 13 NS
required chin lift. Before sedation, the patients’ average BMI 23.2 + 1.9 30.9 + 3.6 b0.0001
systolic BP (SBP) were significantly increased ( P b 0.0001) sec/ss/drr 82% 78% NS
compared with those obtained at the preoperative evalua- No ebm/hm/cop 78% 78% NS
Brief LOC 6% 7% NS
tion. Immediately after sedation and regional block, pa-
RD-FC 27% 28% NS
tients’ SBP decreased 6% from their baseline ( P b 0.005). Brief apnea 2% 2% NS
Although 50% of the patients had recall of the regional Brief O2 6% 5% NS
block, it was considered nonstressful and acceptable. Of desaturation
the 39 patients who underwent procedures less than 30 min- Need for airway 1% 1% NS
utes, only 7 (18%) required midazolam for anxiolysis. Patient support
and surgeon satisfaction scores were 9.87 F 0.68 and 9.6 F BL-BP (mmHg) 135.6 F 23.3 142.3 F 22.3 NS
0.88, respectively. SBP (pre-bl) 17 F 22 9.6 F 24 NS
In these 89 patients, 40 were considered overweight or (mmHg)
obese with a BMI greater than 26. There were no significant SBP (post-bl) 3.22 F 20.73 13.70 F 22.37 NS
differences in age or sex between the overweight/obese and (mmHg)
N/V 0.0% 0.0% NS
normal weight groups. However, the difference in BMI was
Had recall 51% 50% NS
significant ( P b 0.0001) (Table 3). Seventy-eight percent of Patient 9.7 + 0.5 9.8 + 0.6 NS
patients in the overweight/obese group showed all 3 signs of evaluation
sedation, comparable to that in the normal weight group score
(82%, P = 0.79). There were no significant differences in Surgeon 9.6 + 0.8 9.6 + 0.7 NS
patient responses to the regional block, in respiratory or evaluation
hemodynamic changes between the 2 groups (Table 3). score
sec indicates spontaneous eye closure; ss, sluggish speech; drr, decreased
respiratory rate; ebm, eyebrow movement; hm, head movement; cop,
4. Discussion complaint of pain; LOC, loss of consciousness; RD-FC, respiratory
depression but able to follow command; BL-BP, baseline blood pressure;
SBP (pre-bl), SBP difference between baseline and that before sedation;
Ideally, a sedation/analgesic technique should provide
SBP (post-bl), difference between baseline and that after sedation.
anxiolysis, amnesia, and profound analgesia while main-
MAC in ophthalmic surgery
were ready in 3 to 5 minutes for the nerve block. After the
procedure, patients did not need to go to the Postanesthesia
Care Unit but were discharged to the preoperative area for
discharge home.
Obesity presents a challenge for anesthesiologists during
monitored anesthesia care procedures not only because of
potentially higher risks of airway and hemodynamic
complications, but also because of difficulty determining
appropriate doses. Using patients’ weight for dosing of
propofol and/or narcotics may potentially result in an
overdose and excessive hemodynamic changes [11], where-
as using the IBW might lead to an underdose. Salihoglu et
al [13] showed similar effects in controlling the hemody-
namic response to tracheal intubation in morbidly obese
patients when alfentanil, fentanyl, and remifentanil were
given with corrected weight ([0.4  excess height] + ideal
weight) [11]. In our study, by using the IBW plus 30% of
the difference between real weight and IBW for drug
dosing, we provided excellent sedation and analgesia that
was comparable to patients of normal weight.
Alfentanil is compatible in combination with propofol or
lidocaine [14,15]. No precipitation, venous catheter occlu-
sion, or adverse pharmacologic effects have been observed
in our use of the 6-2-2 mixture. However, further study is
necessary to identify any pharmacologic changes of
alfentanil, propofol, or lidocaine when mixed together.
References
[1] Atanackovic D, Brunner-Weinzierl MC, Kroger H, Serke S, Deter HC.
Acute psychological stress simultaneously alter hormone levels,
recruitment of lymphocytes subsets, and production of reactive
oxygen species. Immunol Invest 2002;31(2):73 - 91.
117
[2] Larson MR, Ader R, Moynihan JA. Heart rate, neuroendocrine, and
immunological reactivity in response to an acute laboratory stressor.
Psychosom Med 2001;63(3):493 - 501.
[3] Ogawa K, Hirai M, Katsube T, et al. Suppression of cellular immunity
by surgical stress. Surgery 2000;127(3):329 - 36.
[4] Greisen J, Juhl CB, et al. Acute pain induces insulin resistance in
humans. Anesthesiology 2001;95(3):578 - 84.
[5] Logan HL, Lutgendorf S, Kirchner HL, Rivera EM, Lubaroff D. Pain
and immunologic response to root canal treatment and subsequent
health outcomes. Psychosom Med 2001;63(3):453 - 62.
[6] Avramov MN, White PF. Use of alfentanil and propofol for outpatient
monitored anesthesia care: determining the optimal dosing regimen.
Anesth Analg 1997;85:566 - 72.
[7] Badrinath S, Avramov MN, Shadrick M, Witt TR, Ivankovich AD.
The use of a ketamine-propofol combination during monitored
anesthesia care. Anesth Analg 2000;90(4):858 - 62.
[8] Taylor E, Ghouri AF, White PF. Midazolam in combination with
propofol for sedation during local anesthesia. J Clin Anesth 1992;
4(3):213 - 6.
[9] Yee JB, Burns TA, Mann JM, Crandall AS. Propofol and alfentanil for
sedation during placement of retrobulbar block for cataract surgery.
J Clin Anesth 1996;8(8):623 - 6.
[10] Stead SW, Beatie CD, Keyes MA. In: Longnecker DE, Tinker JH,
Morgan GE, editors. Chapter 83: Anesthesia for ophthalmic
surgery, principles and practice of anesthesiology. 2nd ed. Mosby,
1998. p. 2181 - 99.
[11] Servin F, Farinotti R, Haberer JP, Desmonts JM. Propofol infusion for
maintenance of anesthesia in morbidly obese patients receiving nitrous
oxide. Anesthesiology 1993;78(4):657 - 65.
[12] Chernik DA, Gillings D, Laine H, et al. Validity and reliability of the
Observer’s Assessment of Alertness/Sedation Scale: study with
intravenous midazolam. J Clin Psychopharmacol 1990;10:244 - 51.
[13] Salihoglu Z, Demiroluk S, Demirkiran MA, Kose Y. Comparison of
effects of remifentanil, alfentanil and fentanyl on cardiovascular
responses to tracheal intubation in morbidly obese patients. Eur J
Anaesthesiol 2002;19(2):125 - 8.
[14] Taylor IN, Kenny GN, Glen JB. Pharmacodynamic stability of a
mixture of propofol and alfentanil. Br J Anaesth 1993;69(2):382 - 3.
[15] Trissel LA. Handbook on injectable drugs. 12th ed American Society
of Health-System Pharmacists, 2003. p. 20.