ISSN NUMBER: 1938-7172
Issue 4.11

Michael A. Fiedler, PhD, CRNA

Contributing Editors:
Penelope S Benedik, PhD, CRNA, RRT
Mary A Golinski, PhD, CRNA
Gerard Hogan Jr., DNSc, CRNA
Alfred E Lupien, PhD, CRNA
Lisa Osborne, PhD, CRNA
Dennis Spence, PhD, CRNA
Cassy Taylor, DNP, DMP, CRNA
Steven R Wooden, MS, CRNA

Assistant Editor
Jessica Floyd, BS

A Publication of Lifelong Learning, LLC © Copyright 2010

New health information becomes available constantly. While we strive to provide accurate information, factual and typographical errors may occur. The authors, editors, publisher, and Lifelong Learning, LLC is/are not responsible for any errors or omissions in the information presented. We endeavor to provide accurate information helpful in your clinical practice. Remember, though, that there is a lot of information out there and we are only presenting some of it here. Also, the comments of contributors represent their personal views, colored by their knowledge, understanding, experience, and judgment which may differ from yours. Their comments are written without knowing details of the clinical situation in which you may apply the information. In the end, your clinical decisions should be based upon your best judgment for each specific patient situation. We do not accept responsibility for clinical decisions or outcomes.

Table of Contents

Obstructive sleep apnea syndrome and postoperative complications: clinical use of the stop-bang questionnaire

Efficacy of clevidipine in controlling perioperative hypertension in neurosurgical patients, initial single-center experience

Gabapentin improves postcesarean delivery pain management: a randomized, placebo-controlled trial

The effect of additional propofol on intubating conditions

Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery

Delayed radicular pain following two large volume epidural blood patches for post-lumbar puncture headache: a case report

Attention subscribers licensed in Alabama, Alaska, Idaho, Kentucky, Nevada, and New Mexico: This issue contains 1 PHARMACOLOGY specific CE credit.

Obstructive sleep apnea syndrome and postoperative complications: clinical use of the stop-bang questionnaire

Arch Otolaryngol Head Neck Surg 2010;136:1020-24

Vasu TS, Doghramji K, Cavallazzi R et al


Purpose The purpose of this study was to determine if a higher score on the STOP-BANG questionnaire predicted higher rates of postoperative complications after elective surgery at a tertiary care facility.

Background Obstructive sleep apnea syndrome (OSAS) has a prevalence of 5% to 9% in the general population. During the perioperative period anesthetic and analgesic agents can exacerbate the cardiorespiratory consequences of OSAS, potentially increasing the risk for postoperative complications. Therefore, it is essential to identify patients with OSAS. 

The gold standard for diagnosis of OSAS is nocturnal polysomnography; however many patients presenting for elective surgery with suspected OSAS do not present with sleep study results. Recently the STOP-BANG questionnaire (Snoring: yes or no, Tiredness during daytime, Observed apnea, High Blood Pressure, BMI < 35 kg/m2, Age > 50, Neck circumference > 40 cm or 15.75 in, and Male Gender) has been demonstrated to be a valid screening questionnaire to identify surgical patients at high risk for OSAS (score ≥ 3 high risk for OSAS).

Methodology This was an historical cohort study of 135 patients presenting for elective surgery at a tertiary care facility. All subjects were administered the STOP-BANG questionnaire preoperatively. Clinical records were retrospectively reviewed by investigators blinded to questionnaire results. Data recorded included: demographic data, type of surgery, ASA class, duration of surgery, use of neuromuscular blockers, comorbidities, length of stay, and serum albumin and creatinine level. Patients with elevated creatinine or low albumin levels were excluded. The primary outcomes were the presence or absence of new onset atrial fibrillation, systemic hypotension (systolic BP < 90 mmHg that required aggressive therapy), myocardial infarction, or pulmonary complications (hypoxemia, atelectasis, pulmonary embolism or pneumonia). Multiple logistic regression was used to analyze the results. Accuracy of the STOP-BANG was determined by analyzing the area under the receiver operating characteristic (ROC) curve. A P < 0.05 was considered significant.

Result A total of 135 patients were included in the study. The mean age was 57.9 (14.4) yrs, with n = 60 (44.4%) being men. Approximately one-fourth (25.2%) of patients were obese (BMI ≥ 30 kg/m2). A little less than half (n = 56, 41.5%) were high risk for OSAS based on their STOP-BANG results (score of 3 or higher). Orthopedic (n = 51, 37.8%) operations were the most common surgical procedure, followed by Head and Neck (n = 23, 17%), Abdominal (n = 19, 14.1%), Gynecologic (n = 12, 8.9%) and Genitourinary (n = 9, 6.7%). Most operations were performed under general anesthesia (n = 116, 85.9%), with a little more than one-third being high-risk surgical procedures (n = 48, 35.5%). Neuromuscular blockers were used in a majority of patients (n = 77, 59.2%).

Patients at high risk for OSAS (n = 56) were older, more likely to be obese males with a higher ASA class, and a potential difficult airway when compared to patients at low risk (n = 79) for OSAS based on the STOP-BANG results (Table 1).



Table 1. Demographics


High Risk for OSAS (n = 56)

Low Risk for OSAS (n = 79)

Age in yrs, mean (SD)

64.7 (10.1)

53 (15.1) 

Male Gender

38 (67.9%)

22 (27.8%)

BMI > 30 kg/m2

24 (42.8%)

10 (12.6%)

ASA Class 3

36 (64.3%)

30 (38%)

Potential Difficult Airway (Mallampati 3 or 4)

26 (46.4%)

12 (15.2%)








37 (66.1%)

9 (16.1%)

5 (8.9%)

4 (7.1%)

2 (3.6%)


22 (27.8%)

5 (6.3%)

3 (3.8%)

5 (6.3%)

1 (1.3%)

Length of stay (days)

3.6 (3.6)

2.1 (1.4)


A total of 12 complications occurred (8.9%). Only one patient at low risk for OSAS had a complication (female patient, 74 yrs old, orthopedic surgery; pneumonia). The type of complications that occurred in high risk patients included:

  1. hypoxemia with atelectasis (n = 5)
  2. hypotension (n =2)
  3. hypoxemia with pulmonary embolism (n = 1)
  4. pneumonia (n =1)
  5. atrial fibrillation (n = 1)
  6. pneumonia with respiratory failure (n = 1).

Complication rates were higher in patients older than 60 years (14.1% vs. 4.2%, P = 0.04), obese patients (17.6% vs. 5.9%, P = 0.04) and higher ASA Class (Class 3 or higher: 16.7% vs. 1.4%, P = 0.001). Patients that were high risk for OSAS were 11.4 times more likely to experience a postoperative complication (95% CI: 1.18-110.47, P = 0.03). Likewise, patients who were ASA Class ≥ 3 were 8.9 times more likely to experience a postoperative cardiopulmonary complication (95% CI: 1.04-75.71, P = 0.04). Obesity (OR 1.64, 95% CI: 0.42-6.41, P = 0.47) and age > 60 years (OR 1.01, 95% CI: 0.21-5.02, P = 0.98) were not associated with higher risk of complications. The STOP-BANG had high sensitivity (91.7%) and moderate specificity (63.4%) to predict postoperative complications (Table 2).



Table 2. Accuracy of STOP-BANG >3 to Predict Postoperative Complications


 91.7% (95% CI, 61.5%-99.8%)


 63.4% (95% CI, 54.3%-71.9%)

 Positive Predictive Value

 19.6% (95% CI, 10.2%-32.4%)

 Negative Predictive Value

 98.7% (95% CI, 93.1%-100%)

 ROC Area under the curve



Conclusion The STOP-BANG obstructive sleep apnea screening questionnaire can be helpful in identifying surgical patients at high risk for postoperative cardiac and pulmonary complications.



Obstructive sleep apnea is one of the most significant problems faced by anesthesia providers. As one can see from these results, OSAS is associated with a number of comorbidities which influence our anesthetic plan and postoperative outcomes. The problem is only going to get worse as our society ages and gets more obese. This was a good study because it demonstrated that the STOP-BANG is a simple and accurate tool for identifying patients at risk for postoperative complications. My guess is many of our readers have started to use it, and if not I would recommend incorporating it into your preoperative interview or screening process. It is easier and cheaper than getting a sleep study and can help you formulate an anesthetic plan that minimizes cardiopulmonary complications.

In this study the STOP-BANG was highly sensitive (91.7%) but only moderately specific (63.4%) for predicting postoperative complications. Therefore in this study 91.7% of patients with a postoperative complication had a STOP-BANG score of 3 or more. However, only 63.4% of patients who were identified as being low risk for OSA (score less than 3) did not develop a postoperative complication. So what do these results tell us? Just because a patient is identified as low risk based on the STOP-BANG does not necessarily mean they will not develop a postoperative complication. What this study demonstrates is that a patient at high risk for OSA based on the STOP-BANG is more likely to develop cardiopulmonary complications. 

There are a lot of other reasons for postoperative complications (i.e., pulmonary embolism after total joint surgery), and not all of them will be associated with OSA. The instrument is cheap and easy to administer and the potential benefits are great, therefore I would recommend its use. I would like to see large, multi-site, studies performed using this instrument, especially in military institutions where the surgical population is younger and healthier, to see if it predicts postoperative complications.


Dennis Spence, PhD, CRNA

The views expressed in this article are those of the author and do not reflect official policy or position of the Department of the Navy, the Department of Defense, the Uniformed Services University of the Health Sciences,  or the United States Government.

© Copyright 2010 Anesthesia Abstracts · Volume 4 Number 11, November 30, 2010

Neurosurgical Anesthesia
Efficacy of clevidipine in controlling perioperative hypertension in neurosurgical patients, initial single-center experience

J Neurosurg Anesthesiol 2010:22;330-335

Bekker A, Didehvar S, Kim S, Golfinos J, Parker E, Sapson A, Haile M, Kline R, Lee M


Purpose The purpose of this study was to evaluate the efficacy of clevidipine (Cleviprex); a rapid acting, vascular-selective, L-type calcium channel antagonist; to reduce systolic blood pressure (SBP) for those undergoing intracranial surgery, where hypertension could have deleterious effects.

Background Systolic hypertension during intracranial neurosurgical procedures is estimated to occur quite frequently. It is associated with cerebral bleeds, cerebral edema, increased intracranial pressure and a prolonged hospital length of stay. It has been reported that >50% of neurosurgical patients experiencing peri-operative hypertension require prompt pharmacologic treatment. It is also felt that many of the current medications used do not possess the specific profiles that are required and their side effects can be especially harmful to this patient population. For example, labetalol is often used but its prolonged duration of action combined with a slower onset of peak effect and a lack of predictability in dose requirements, is problematic. Esmolol is often selected but appears to be most beneficial in treating hypertension associated with tachycardia and not as effective when the high blood pressure is related to an increase in systemic vascular resistance (SVR). Beta blockers can cause bradycardia, conduction delays, left ventricular dysfunction, and bronchospasm, and are therefore not considered therapeutic for many. It has been well established that sodium nitroprusside, nitroglycerin and hydralazine create dilation of the cerebral capacitance vessels and therefore may increase intracranial pressure. Nicardipine, a dihydropyridine calcium channel blocker, has been studied, but its pharmacokinetic profile limits its use in this population.

For obvious reasons, short acting drugs are preferred. Clevidipine is a rapid acting, vascular selective, L- type calcium channel antagonist that lowers blood pressure by reducing SVR. It is rapidly hydrolyzed by plasma esterases and its elimination is independent of liver and kidney function. The half- life of clevidipine is < 1 minute. It can be easily titrated to the desired effect. Due to its unique profile, it may offer significant advantages for use in neurosurgical patients.

Methodology The study was conducted as an open label, prospective, observational clinical trial to evaluate the efficacy of clevidipine in treating hypertension in the neurosurgical patient. Specific inclusion criteria included those >21 years, with normal laboratory values who were scheduled for elective craniotomy under general anesthesia.

A standardized anesthetic regime was used for all enrolled. The primary endpoint of the study was the proportion of those in whom systolic blood pressure could be controlled with clevidipine as the sole antihypertensive agent. Secondary endpoints included the time required to reduce SBP to below 130 mm Hg, the dose of clevidipine required to achieve the target SBP, and the peri-operative use of other antihypertensive and vasoactive drugs.

Hemodynamic events were defined as follows:

  1. hypertension:  systolic BP > 130 mm Hg
  2. hypotension:   SBP < 90 mm Hg (incremental doses of ephedrine & phenylephrine)
  3. bradycardia:    HR < 40 bpm (glycopyrrolate as primary treatment)
  4. tachycardia:    HR > 90 bpm  and not associated with pain (metoprolol as primary treatment) 

The primary goal of hemodynamic management included: maintaining an SBP between 90-130 mm Hg and HR between 40-90 bpm. If blood pressure increases during surgery were obviously related to painful stimuli, opioids were adjusted appropriately. Clevidipine (0.5 mg/mL in 20% lipid solution) was used as a primary antihypertensive drug during surgery and in the PACU for the first 90 minutes. The drug infusion was initiated at 5-10 mg/h if the SBP was >130 mm Hg and titrated to a maximum dose of 50 mg/h. If hypertension persisted after treatment for more than 20 minutes, alternative antihypertensive agents were used at the discretion of the provider.

Results A total of 22 patients were consented and enrolled. Only one did not require antihypertensive treatment. The majority of the surgical procedures were craniotomy for tumor (14/21) and the majority of the patients were ASA II (12/21). A clevidipine infusion was sufficient to control BP episodes in 17/21 of those enrolled (the primary outcome variable). Three patients required treatment with labetalol in addition to the study drug and one patient received a combination of labetalol and hydralazine. The following summarizes other secondary outcome variables:

  • Target SBP was attained within 5 minutes of initiating treatment in 14/21 hypertensive episodes
  • Target SBP was attained within 15 minutes in 22/28 hypertensive episodes
  • The total amount of clevidipine to maintain target SBP was 7.6 + 10.1 mg in the intra-operative period
  • The total amount of clevidipine to maintain target SBP was 15.3 + 18.8 mg in the PACU
  • Short term infusions of clevidipine treated brief hypertensive episodes during induction (1.4 + 0.7 mg) and maintenance of anesthesia (2.9 + 5.8 mg)
  • During emergence from anesthesia, higher doses of clevidipine were administered for persistent elevated SBP (5.7 + 5.8 mg)
  • 16/21 patients received concomitant metoprolol for tachycardia not related to elevated SBP
  • Neither rescue antihypertensive agents nor vasoactive drugs were required during the first 90 minutes in PACU
  • 22 episodes of transient hypotension either post induction, during maintenance of anesthesia, or during emergence required treatment with:
    • fluid boluses
    • a decrease in propofol or remifentanil infusions
    • ephedrine and/or phenylephrine


Conclusion Keeping in mind the small sample size, Clevidipine was administered as the sole antihypertensive agent in the majority of patients, controlling SBP and maintaining it within the selected ‘safe’ range. Adding labetalol allowed for a complete response in all patients. No serious adverse events were attributed to the study drug. This study described the first application of clevidipine in the neurosurgical population; a population where acute hypertension from various causes can be detrimental.



Maintaining hemodynamic stability and preventing acute hypertensive episodes in the fragile neurosurgical population can be extremely challenging for the anesthetist. When acute hypertension occurs from increased activity of the sympathetic nervous system, or from any other causes, action must be taken immediately and drugs must be chosen that have an extremely quick onset. If the body’s response to a select medication is ‘too much’ or ‘lasts too long’ or if the drug causes the blood pressure to drop precipitously and out of a safe range, the outcomes can be just as bad as those from the acute hypertensive episode!  Using high or higher doses of opioids in the neurosurgical patient can create issues, especially if upon the completion of the procedure, a complete neurologic assessment is necessary yet the patient is narcotized. Clevidipine appears to offer advantages in this specific population and its unique pharmacokinetic profile lends itself towards a safety profile that shows great potential.

Mary A Golinski, PhD, CRNA

The reader is referred to the following to learn more about clevidipine:

© Copyright 2010 Anesthesia Abstracts · Volume 4 Number 11, November 30, 2010

Gabapentin improves postcesarean delivery pain management: a randomized, placebo-controlled trial

Anesth Analg 2011;112:167-73

Moore A, Costello J, Wieczorek P, Shah V, Taddio A, Carvalho JCA


Purpose To evaluate the efficacy of gabapentin 600 mg administered one hour prior to cesarean delivery on decreasing postoperative pain.

Background Postoperative pain after cesarean delivery can decrease maternal-infant bonding and limit the mother’s ability to care for the newborn. Typically, a multimodal regimen consisting of nonsteroidal anti-inflammatory agents, neuraxial opioids, and acetaminophen are administered to decrease postoperative pain. However, this regimen may be ineffective in some patients, and up to 12.3% of women may develop chronic pain. Multiple studies have demonstrated that gabapentin administered as a single preoperative dose decreases postoperative pain after a variety of surgical procedures, and some preliminary research suggests it may reduce the incidence of persistent pain after abdominal hysterectomy. Gabapentin purportedly exerts its analgesic properties by binding to presynaptic voltage-gated calcium channels resulting in decreased release of excitatory neurotransmitters. Registry data indicates that gabapentin administered during pregnancy is not associated with adverse maternal or fetal outcomes.

Methodology This was a randomized, double-blind, placebo controlled trial evaluating the efficacy of 600 mg gabapentin when combined with a multimodal regimen for decreasing postoperative pain. All subjects were managed with a standard anesthetic protocol consisting of spinal anesthesia with 0.75% bupivacaine, fentanyl 10 µg, and preservative free morphine 100 µg. After surgery patients received ketorolac 30 mg IV and acetaminophen 1 gm pr. In the PACU they received morphine prn, and on the ward oral diclofenac 50 mg Q 8 hr and oral acetaminophen 1 gm Q6 hr were administered for 72 hrs. Breakthrough pain was treated with SQ morphine 2 mg every 4 hr prn. Opioid-related side effects were treated with a standardized protocol.

Data collection included maternal and neonatal demographics, maternal and umbilical artery and venous gabapentin levels (only in the first 26 patients). Postoperative pain was scored at rest and with movement (0-100 mm visual analogue scale). The severity of pruritus, nausea, vomiting, sedation, and dizziness was scored with a 4-point Likert scale (none = 0, mild = 1, moderate = 2 or severe = 3). Satisfaction with pain management was scored on a 0 to 10 numeric scale. All parameters were evaluated at 6, 12, 24, and 48 hours after induction of spinal anesthesia. Supplemental opioids and medications to treat opioid-related side effects were recorded. At 3 months patients were contacted to evaluate the incidence of chronic pain.

The primary outcome was pain with movement at 24 hours, and secondary outcomes included patient satisfaction, opioid and gabapentin side effects, and incidence of chronic pain. Chronic  pain was evaluated as presence of persistent pain, any abnormal wound sensation, pain limiting daily function, and pain medication requirement at 3 months. Additionally, pain severity was evaluated with a numeric rating scale. Inferential and descriptive statistics were used to analyze the results. Power analysis determined that 50 subjects per group would be needed to show a 30% reduction in pain scores with movement. An interim analysis was planned after enrollment of every 26 subjects.

Result One hundred and sixty six parturients were asked to enroll in the study but only 46 chose to participate (23 in each group). Two subjects were excluded from the gabapentin group; one for excessive sedation and hypoglycemia postoperatively and one who did not have a cesarean delivery (gabapentin group n = 21; control group n = 23). Because of the extremely low recruitment rate and movement of study personnel to other facilities, the study was discontinued after 46 patients. 

Baseline maternal and neonatal demographics were similar between the two groups. Pain scores with movement were significantly lower in the gabapentin group compared to the control group at all time points (P < 0.021). Pain with movement at 24 hours was 21 mm (95% CI: 13-29) in the gabapentin group and 41 mm (95% CI: 32-51) in the placebo group (P = 0.001). However pain scores were only significantly lower at rest at 6 (P = 0.02) and 12 hours (P = 0.02) in the gabapentin group, and similar to the control group at 24 and 48 hours. Satisfaction with pain management scores were significantly higher in the gabapentin group at 6 hrs (median = 10 vs 8; P = 0.01) and 12 hrs (median = 10 vs 8; P = 0.004), respectively.

Opioid consumption was similar between the groups. The incidence and severity of nausea, vomiting, pruritus, and dizziness were similar between the two groups. There was a higher, though not statistically significant difference, in the number of subjects experiencing nausea in the gabapentin group (57% vs. 34%; P = 0.14). In contrast more subjects in the control group experienced pruritus when compared to the gabapentin group (96% vs. 76%; P = 0.09). Severe sedation, defined as a score of 2 or 3, was 19% in the gabapentin group and 0% in the control group; significantly higher in the gabapentin group (P = 0.04). Exploratory analysis revealed that the severe sedation most likely occurred within the first 24 hours. No significant differences in the incidence of chronic pain symptoms or opioid consumption was noted at 3 months.

Conclusion A single preoperative dose of 600 mg gabapentin has efficacy in decreasing postoperative pain and increasing patient satisfaction with pain management after cesarean delivery. However, gabapentin was associated with a higher incidence of severe sedation within the first 24 hours when compared to placebo. No adverse neonatal effects were noted. Further studies are needed to determine the optimal dose, duration of treatment, and safety in patients undergoing cesarean delivery.



This is the first study ever published on the addition of gabapentin to a multimodal analgesic regimen after cesarean delivery. I think gabapentin is a promising drug that has shown efficacy in decreasing postoperative pain and reducing opioid consumption, and there is some preliminary evidence to suggest it may be helpful in reducing the incidence of chronic pain in other surgical populations. However, it is associated with a significantly higher incidence of sedation and dizziness. While dizziness rates were similar between the two groups, more subjects did report severe sedation in the first 24 hours. I am skeptical about the findings for dizziness because most patients probably did not ambulate for several hours after the spinal anesthetic so it it is possible the investigators were not able to capture this effect. I would have liked to have seen the investigators measure overall satisfaction or satisfaction with side effects because this would be more clinically relevant and help anesthesia providers determine if they would administer gabapentin preoperatively for cesarean delivery. Furthermore, I don't think a difference of a satisfaction score of 8 and 10 is clinically significant because most would consider these rates pretty good.

One interesting finding was the higher rates of nausea and lower pruritus in the gabapentin group. There were no statistically significant differences, however the study was terminated early due to poor recruitment so I suspect with a larger sample that differences might have been found between the groups. The higher nausea could be related to the common side effect of dizziness with gabapentin. The 20% lower rate of pruritus in the gabapentin group could be related to the effect gabapentin has in the dorsal horn where intrathecal morphine exerts its effect. Maybe gabapentin works synergistically with intrathecal opioids but is able to work centrally to antagonize the opioid-related side effect of dizziness. On the other hand, it could be that patients given gabapentin are just more sedated and thus less likely to report side effects. Future studies are needed to explore this hypothesis.

Despite the positive findings for decreased pain in this study, I do not think gabapentin will be used routinely after cesarean delivery. Many parturients do not like taking additional medications out of real or unfounded fears of effects on themselves or the newborn. The poor recruitment rate of 27% I think supports this. In my opinion, I think we do a very good job overall in managing pain after cesarean delivery with neuraxial morphine in a multimodal regimen that includes around the clock NSAIDS, acetaminophen, and prn opioids. The investigators in fact found the need for supplemental opioids was very low and similar between the groups, which tells me either moms do not want to take additional drugs or the analgesic regimen was working. What future investigators need to explore are interventions focused on decreasing the opioid-related side effects of pruritus and nausea after neuraxial morphine.

Dennis Spence, PhD, CRNA

The first interim analysis showed the mean 24 hr pain with movement score to be 41 (range: 26-56) in the control group and only 18 (8-29) in the gabapentin group (23-mm difference in pain with movement).

The views expressed in this article are those of the author and do not reflect official policy or position of the Department of the Navy, the Department of Defense, the Uniformed Services University of the Health Sciences,  or the United States Government.

© Copyright 2010 Anesthesia Abstracts · Volume 4 Number 11, November 30, 2010

The effect of additional propofol on intubating conditions

J Clin Anesth 2010;22:603-607

Kwon MA, Kim SK, Jeon DG, Song JK, Kim WI


Purpose The purpose of this study was to evaluate the effects of divided doses of propofol prior to intubation on intubating conditions and hemodynamics.

Background Propofol improves intubating conditions in a dose dependent manner. Propofol does not potentiate non-depolarizing neuromuscular blockade and the mechanism by which it causes relaxation of laryngeal muscles is unclear. While larger induction doses of propofol produce better intubating conditions, they also result in hypotension and, at times, reduced heart rate as well. These hemodynamic effects delay the transit of non-depolarizing muscle relaxants to the neuromuscular junction, slowing the onset of paralysis.

Methodology This prospective, randomized, double-blind study included 102 ASA physical status I and II patients, 18 years to 70 years old, scheduled for elective procedures. Exclusion criteria included an abnormal airway, severe cardiovascular disease, and a systolic blood pressure greater than 180 mmHg. 

Patients were not premedicated. General anesthesia was standardized, except for the dose and timing of propofol administration. Patients were randomly assigned to one of three groups. The propofol 1.5 group received a single dose of 1.5 mg/kg propofol. The propofol 1.5+0.5 mg/kg group received an induction dose of 1.5 mg/kg propofol followed by an additional 0.5 mg/kg propofol 45 seconds before intubation. The propofol 2.0 group received a single dose of 2.0 mg/kg propofol for induction. All patients received 1.5 µg/kg fentanyl prior to induction of general anesthesia. In addition to standard monitoring, BP was monitored invasively. Following induction of general anesthesia, rocuronium 0.6 mg/kg was administered, followed by inhalation of 100% oxygen and 6% sevoflurane. In the propofol 1.5+0.5 group, the second dose of propofol was administered 45 seconds after rocuronium. In the other two groups, an equal volume of normal saline was administered in lieu of the second dose of propofol. Syringes were covered with an opaque material to prevent the anesthetist from knowing whether propofol or saline had been administered.

Intubating conditions were categorized as excellent, good, poor, or impossible. “Excellent” conditions included a relaxed jaw, vocal cords that were abducted and immobile, and no diaphragm movement. “Good: intubating conditions allowed for some diaphragm movement. “Poor” intubating conditions included movement of the vocal cords and coughing or bucking. “Impossible” intubating conditions were present when the jaw was not relaxed and the vocal cords were closed.

Plasma and effect site concentrations of propofol at intubation were estimated. Statistical analysis was appropriate.

Result The median time from administration of the induction dose of propofol to loss of consciousness was 24 seconds in the propofol 1.5 group, 29 seconds in the propofol 1.5+0.5 group, and 18 seconds in the propofol 2.0 group (P < 0.004 propofol 2.0 group versus other groups). The MAC of sevoflurane was similar in each group during intubation. Estimated plasma concentrations of propofol at intubation were 6.7 µg/mL in the propofol 1.5+0.5 group compared with only 2.6 µg/mL in the propofol 1.5 group and 2.7 µg/mL in the propofol 2.0 group (P < 0.001). Estimated effect site concentrations at intubation were 4.7 µg/mL in the propofol 1.5 group, 6.1 µg/mL in the propofol 1.5+0.5 group, and 5.7 µg/mL in the propofol 2.0 group (P < 0.001).

The number of patients with excellent or good intubating conditions was significantly higher in the propofol 1.5+0.5 group compared to either the propofol 1.5 or the propofol 2.0 group (P < 0.004). Of the 34 patients in each group, 31 in the propofol 1.5+0.5 group had excellent intubating conditions, compared to only 10 patients in the propofol 2.0 group and 8 patients in the propofol 1.5 group. Good intubating conditions occurred at about the same rate in each group. Poor intubating conditions occurred in only 3 patients in the propofol 1.5+0.5 group compared to 14 and 13 patients respectfully in the propofol 2.0 group and propofol 1.5 group.

There were no significant differences in hemodynamics in any of the groups at baseline. However, 2 patients in groups propofol 1.5 and propofol 2.0 had an MAP less than 60 mmHg that required treatment. One patient in the propofol 1.5 group and 3 patients in the propofol 2.0 group also had a heart rate less than 50 bpm.

Conclusion Inducing general anesthesia with 1.5 mg/kg of propofol followed by an additional 0.5 mg/kg propofol before intubation resulted in better intubating conditions and higher estimated plasma and effect site concentrations of propofol then administering either 1.5 or 2.0 mg/kg of propofol alone for induction of general anesthesia. Dividing the induction dose of propofol in this manner does not result in undesirable hemodynamic effects but does reduce the incidence of hypotension requiring treatment.



Early in my career I worked with an exceptionally skilled anesthetist whose motto was “neater, sweeter, slicker, quicker.” John’s goal was not only to provide a quality anesthetic, but to work so smoothly that it looked like a performance. He would’ve loved to this article.

A superficial look at this article leaves you thinking, “what's the difference whether I give all the propofol at once or save some of it to give a few seconds later just before I intubate?” But there are two aspects of this study which deserve closer attention. First, we have to think about the effects of a normal intubating dose of propofol on blood pressure and cardiac output. We know from other studies that administering something that increases cardiac output (e.g. ephedrine) at the same time that we give a non-depolarizing muscle relaxant speeds the onset of paralysis. Quite simply, increasing cardiac output gets the non-depolarizer to the site of action more quickly. It stands to reason, then, that reducing blood pressure and cardiac output with a full intubating dose of propofol may slow the onset of neuromuscular blockade because the non-depolarizer gets to the neuromuscular junction more slowly. Administering propofol in divided doses was shown in this study to reduce the incidence of hypotension and bradycardia, thus preserving cardiac output and allowing the rocuronium to reach the neuromuscular junction more quickly. Secondly, we'd like to give as large a dose of propofol as possible because larger doses provide better intubating conditions and prevent sympathetic responses to laryngoscopy and intubation. But doing so often results in undesirable decreases in blood pressure. This study showed that administering the propofol in two partial doses resulted in higher estimated plasma levels of propofol at the time of intubation while at the same time attenuating any decreases in blood pressure and heart rate. A win win; better intubating conditions, better hemodynamics.

We can all go to the OR tomorrow and induced general anesthesia with propofol the same way we always have. But if we want to do the job just a little bit better we should heed what this article has to teach us. Doing so will take a perfectly good anesthetic and make it into something more like a performance; something “neater, sweeter, slicker, quicker.”

Michael A. Fiedler, PhD, CRNA

© Copyright 2010 Anesthesia Abstracts · Volume 4 Number 11, November 30, 2010

Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery

Anesthesiology 2010;113:639-46

Loftus RW, Yeagar MP, Clark JA, Brown JR, Abdu WA, Sengupta DP, Beach ML


Purpose The purpose of this study was to determine the efficacy of a low-dose preventive ketamine bolus and infusion on total 48-hour morphine consumption and acute postoperative pain in opiate-dependent patients undergoing low back surgery. Secondary outcomes included postoperative pain at 24 and 48 hours and at 6 weeks postoperatively.

Background The N-methyl-D-aspartate antagonist ketamine has shown efficacy in decreasing acute postoperative pain and opioid consumption across multiple surgical populations. When used intraoperatively ketamine has been reported to decrease acute postoperative pain and opioid consumption by up to 33% and 20-25%, respectively. However, it is unclear what effect intraoperative ketamine use has on acute postoperative pain and opioid consumption in patients with chronic pain who are opioid dependent.

Methodology This was a prospective, randomized, double-blind, placebo controlled trial evaluating the efficacy of a loading dose of ketamine 0.5 mg/kg followed by an infusion of 10 mcg/kg/min or placebo in adult patients with chronic back pain undergoing lumbar back surgery. Inclusion criteria included a history of daily opioid use for at least 6 weeks and chronic back pain for at least 3 months. Only patients scheduled for admission were enrolled. Exclusion criteria included allergy to ketamine, increased intraocular pressure, uncontrolled hypertension, increased intracranial pressure, a history of psychosis, and pregnancy.

A standardized anesthetic induction and maintenance protocol was used for all patients. All surgeries were performed by only 2 surgeons. Postoperatively all patients received patient controlled analgesia (fentanyl, hydromorphone or morphine) followed by transition to oral medications as needed managed by the surgical service. The primary outcome was total morphine equivalents during the first 48 hours after the procedure; the secondary outcome was visual analogue pain scores at 24 and 48 hours and at 6 weeks. Additionally, 6-week morphine equivalents, hemodynamic changes, duration of PACU and hospital stay, and adjunctive medication use were collected. Descriptive and inferential statistics were used to analyze the results. A P value < 0.05 was considered significant.

Result A total of 102 out of 165 eligible patients were randomized to one of the two groups (ketamine: n = 52; placebo: n = 50). No significant differences in perioperative demographics, surgeon, instrumental fusion, duration of surgery or blood loss were found between the groups. Subjects in the ketamine group had significantly more levels fused (ketamine group: 2.0 ± 0.9 levels vs. placebo group: 1.6 ± 0.9, P = 0.021). The ketamine group also received adjunctive agents such as NSAIDS, nalbuphine, dexamethasone, and/or acetaminophen more often (ketamine group: 26% vs. placebo group: 6%, P = 0.006). Subjects in the ketamine group required significantly less intraoperative morphine equivalents (ketamine group: 51 ± 27 mg vs. placebo group: 67 ± 44 mg, P = 0.034).

Opioid consumption was significantly less in the ketamine group at 24 and 48 hours, and at 6 weeks postoperatively (P< 0.05; Figure 1). Whereas pain scores were significantly less in the PACU (26.7% decrease, P = 0.033) and at 6 weeks (26.2% decrease, P = 0.026) in the ketamine group, they were not different at 24 (P = 0.902) or 48 hours (P = 0.838) (Figure 2). When subjects who received NSAIDS were excluded from the analysis opioid consumption was still lower in the ketamine group; total morphine equivalents at 48 hours (ketamine group: 203 ± 109 mg vs. placebo group: 323 ± 347 mg, P = 0.045). No differences were found between the groups in terms of ketamine or opioid-related side effects (P > 0.05). At 6 weeks antidepressant use was 10.6% less in the ketamine group when compared to the placebo group (P = 0.023). Exploratory analysis revealed that subjects who had higher opioid consumption preoperatively (≥ 0.5 mg/hr) required 55% more morphine equivalents at 24 hours (P = 0.014) and 52% more morphine at 48 hours (P = 0.031), respectively. In subjects with < 0.5 mg/hr preoperative opioid requirement there were no significant differences between groups at either time point.


Figure 1. Comparison of Morphine Equivalents

Results are presented as total milligrams of morphine at 24 and 48 hours, respectively.

The 6-wk total is mean mg/24 h period.

  • P = 0.032 ** P = 0.029 *** P = 0.041
  • Results presented as mean ± SD.




Figure 2. Comparison of Pain Scores

VAS= visual analogue scale for pain evaluated with a 0-100 mm scale.

*P = 0.033 **P = 0.041

Results presented as mean ± SD.


Conclusion Results of this study confirm that intraoperative use of preventive ketamine significantly decreased opioid consumption and pain in patients with chronic low back pain undergoing back surgery. Evidence suggests that ketamine may help reduce chronic post-surgical pain as well. Given the lack of significant side effects, low-dose ketamine (0.5 mg/kg on induction followed by10 mcg/kg/min) should be considered as part of a multi-modal approach to decrease acute pain after painful surgery in patients with chronic pain.



I think this is an important study that demonstrates what many anesthesia providers suspect; that low-dose ketamine regimens can significantly decrease opioid consumption and acute postoperative pain. Now we have some evidence to support its safe use in chronic pain (low back) patients. What is exciting about this study is that the investigators presented preliminary evidence to suggest an intermediate benefit (at 6-weeks postop) on chronic post-surgical pain with this dosing regimen. Exploratory analysis suggests that the decreased opioid consumption within the first 48 hours after low back surgery was only present in patients who consumed moderate amounts of preoperative morphine (at > 0.5 mg/kg or 40 mg by mouth). As the investigators point out, daily consumption of moderate amounts of opioids can lead to opioid-induced hyperalgesia, therefore these results are promising because they suggest ketamine may help reduce hyperalgesia. 

At my facility several of our spine surgeons request TIVA techniques because they are monitoring somatosensory evoked potentials during multi-level fusions. Many times I utilize a combination of propofol and remifentanil, and occasionally find I need to add ketamine to increase the depth of anesthesia while helping to increase the blood pressure. Now with these results I have even more reason to add ketamine.

Dennis Spence, PhD, CRNA

The views expressed in this article are those of the author and do not reflect official policy or position of the Department of the Navy, the Department of Defense, the Uniformed Services University of the Health Sciences,  or the United States Government.

© Copyright 2010 Anesthesia Abstracts · Volume 4 Number 11, November 30, 2010

Regional Anesthesia
Delayed radicular pain following two large volume epidural blood patches for post-lumbar puncture headache: a case report

Pain Physician 2010;13:257-262

Desai M, Dave A, Martin B


Purpose The purpose of this article was to present a case report concerning a potential complication following an epidural blood patch for a post dural puncture headache.

Background Post dural puncture headaches (PDPH) are a common complication following lumbar puncture. They can result in a severe headache when standing, often accompanied by nausea, vomiting, and visual and auditory disturbances. Conservative treatment, including caffeine, fluids, and pain medication is often used. When these conservative treatments do not offer relief, an epidural blood patch with autologous blood is an often successful treatment for PDPH symptoms. These blood patches are most frequently done with a blind, midline epidural needle placement.

Methodology A 29 year old female who underwent diagnostic lumbar puncture with a 20 gauge spinal needle presented 48 hours later with a severe postural, bifrontal, and occipital headache, unresponsive to conservative therapy. She underwent a blind midline epidural blood patch with 20 mL of autologous blood, which only partially resolved her symptoms. About 24 hours later, another blood patch was performed using 20 mL of autologous blood. Within 5 days, the patient started experiencing severe radicular pain with muscle spasms. She was prescribed pregabalin and methylprednilisone. An MRI did not show any significant pathology. Her symptoms diminished within a month and she did not report any residual problems. 

Discussion The most common volume used in an epidural blood patch is usually between 10-20 mL of autologous blood. It is usually injected at or below the site of the original lumbar puncture suspected of causing the PDPH. The reason that an epidural blood patch works is unknown, but there are a number of theories. Those theories include the possibility that the blood will plug the dural puncture site while it heals through normal tissue processes. Another theory is that pressure, resulting from the volume injected, displaces spinal fluid into the cranium and reduces the traction on nerve fibers. Still another theory is that a blood patch reverses vasodilation which decreases cerebral blood flow and deactivates adenosine receptors. Finally, there is a theory that a blood patch blocks the normal lymphatic and arachnoid villae drainage, allowing rapid expansion of spinal fluid volume.

Complications resulting from an epidural blood patch are rare, but issues have been reported. Those issues are acute parasthesias, neck and back pain, temperature elevation, spinal subdural hematoma, intrathecal hematoma, chronic back pain associated with calcification of the blood patch, and arachnoiditis resulting from blood in the intrathecal space. The symptoms associated with this particular case are not part of these more recognized complications, however this particular case included the administration of an unusually high volume of blood (40 mL) over a narrow period of time. It is possible that her transient radiculopathy was caused by compression on the spinal roots emerging from the cauda equina. The pain probably resolved once the clot was absorbed.

Conclusion Epidural blood patches are not risk free. Attention should be paid to needle placement, volume of blood administered, and time frame between repeated injections. While it is difficult to determine why this particular individual developed complications associated with the blood patches, it is possible that lack of attention to one or more of these important issues was a contributing factor.



This was an interesting article, not for the presentation of a relatively benign complication, but for the focus on the process we use to treat a PDPH. I found the review of the various theories of why a blood patch works to be interesting, and I think the presentation of potential complications was another important aspect of this article. Some of the potential complications are very serious and associated with one or more of the three issues for which the author felt attention should be given.

  1. Needle placement:  Should fluoroscopic guidance routinely be used to make sure the epidural needle is placed properly and that blood is not being infused into the intrathecal space?
  2. Volume of blood: Some studies show that as little as 10 mL of blood is sufficient to provide relief from a PDPH, so why should more blood be administered creating a risk of complications associated with compression or calcification of the blood clot?
  3. Time frame between repeat injections: Providers need to be aware that the more volume placed in the epidural space, the more potential created for complications.


In my experience, some providers approach an epidural blood patch without much thought of the risks accompanying the procedure. Although this is a procedure that can be an important tool for the treatment of a painful complication, the process should not be undertaken lightly, and every effort should be made to minimize complications. Use of fluoroscopic guidance to confirm placement of the needle to assure blood is not being injected into the intrathecal space may be the most controversial recommendation. Verification of needle placement is an important aspect for maximizing results and minimizing complications. Most providers with significant experience in placing epidural needles using a loss of resistance technique may find occasions when verification of placement by fluoroscopy is warranted, but do not feel it is necessary in every case. The question that will remain for some time to come is if verification of needle placement by fluoroscopy is necessary in every case. I suspect there are good arguments on both sides of the issue. The other 2 recommendations, administering the lowest volumes necessary to resolve the problem, and allowing time for volume to absorb before attempting a repeat injection, are much less controversial and should be considered seriously by every provider injecting blood into the epidural space.

Steven R Wooden, MS, CRNA



© Copyright 2010 Anesthesia Abstracts · Volume 4 Number 11, November 30, 2010