Acupuncture for Pain and Nausea in the Intensive Care Unit: A Feasibility Study in a Public Safety Net Hospital

Abstract

Objectives:

To explore the feasibility and acceptability of providing acupuncture treatment to relieve pain and nausea symptoms in intensive care unit (ICU) patients.

Design:

Prospective feasibility study.

Settings/Location:

Public safety net hospital with a 20-bed mixed medical/surgical ICU.

Subjects:

Patients from all services admitted to the ICU from November 14, 2014 to April 2015.

Interventions:

Three 20 min acupuncture treatments given for consented patients who were experiencing pain and/or nausea, in addition to usual care.

Outcome measures:

Primary outcomes assessed were the proportion of patients offered acupuncture who accepted it, their perceptions of the effects of acupuncture treatment on pain and nausea, and the incidence of adverse effects related to acupuncture. Secondary outcomes included medication use, ICU and hospital length of stay, and frequency and pattern of Traditional Chinese Medicine (TCM) diagnoses.

Results:

Of the 576 patients admitted to the ICU, 32.2% were deemed eligible for acupuncture and 42% of these (8% of total) received it. Self-reported pain level immediately after treatment decreased from the pain score reported immediately before treatment by 2.36 points.

The majority of patients reported a benefit from acupuncture on symptoms of pain and also an anxiolytic effect. No major adverse effects were reported. There was a significant decrease in morphine usage after each treatment. The most common single TCM diagnosis was Qi and blood stagnation.

Conclusions:

Acupuncture is feasible, safe, and acceptable in an ICU setting by patients from diverse backgrounds.

Introduction

Pain and nausea are two of the most common complaints among intensive care unit (ICU) patients.^1
–3 Recent guidelines suggest that patient stress due to discomfort is a major contributor to noxious ICU experiences, and that pain may contribute to decreased quality of life after ICU admission.⁴

Conventional treatment modalities for pain, in particular, are limited, have numerous side-effects and toxicities, and evidence suggests that nonpharmacological techniques may improve management and outcomes.^1,5
–7

Acupuncture has been identified worldwide as an effective, low-cost intervention for relieving chronic musculoskeletal pain and reducing nausea and vomiting, in part due to its influence on the autonomic nervous system as well as on the release of endogenous opioids and dopamine.^7

–10 Acupuncture has been shown to be effective for postoperative pain and postoperative nausea and vomiting.^11,12 In addition, acupuncture may reduce the requirement for conventional analgesics and antiemetics, without the same side-effect/toxicity profile.^13,14 A recent survey of physicians revealed an overwhelmingly positive attitude toward acupuncture use for pain management.¹⁵ Although acupuncture is commonly used in the outpatient, postoperative, rehabilitation, and oncology settings, there has been very little research performed on acupuncture in an adult ICU in the United States.¹⁶

The aim of this study was to explore the feasibility and acceptability of providing acupuncture treatment to relieve pain and nausea symptoms in ICU patients. Feasibility is defined as the possibility of being accomplished, as measured by the percentage of patients eligible, and acceptability is defined as the capability of being tolerated, as measured by the number of patients completing treatment. The hypotheses of this study are as follows: that patients would be receptive to acupuncture treatment, that it could reduce pain and nausea symptoms, and that it might lower the requirement for conventional pain and nausea medications.

Materials and Methods

Participant recruitment and selection

The Institutional Review Boards at Highland Hospital and the University of California, Berkeley, approved this study HREC No. 2014-IRB14-04083C. This study was conducted at Highland Hospital in Oakland, California, a 230-bed public safety net hospital with a 20-bed mixed medical/surgical ICU. The general study design used for this trial is depicted in Figure 1. Between November 3, 2014, and April 2, 2015, all ICU patients from the medical, surgical, trauma, and neurosurgical services were considered eligible. Research assistants (RAs) consulted with ICU registered nurses (RNs) between 7:00 am and 8:00 am to assess which patients might be eligible to participate. Once patients were identified, the physician of record was contacted and once the physician granted approval, patients were approached about the study. The Institutional Review Board requested that we assess patient eligibility only after each patient had consented to participation. The RAs then excluded patients who were pregnant, unconscious, younger than 18 years old, with an active major psychiatric disease, or likely to be discharged from the hospital within 3 days. As a result, patients who expressed interest and agreed to participate then signed informed consent. Next, patients' charts were reviewed, and participants were further excluded if their absolute neutrophil count was less than 1000 per microliter, platelet count was less than 50,000 per microliter, International Normalized Ratio was greater than 1.7, Partial Thromboplastin Time was greater than 45 sec, if they had a known bleeding disorder, or were receiving therapeutic anticoagulation.

FIG. 1.

Study design. ICU, intensive care unit; TCM, Traditional Chinese Medicine.

Interventions

Acupuncture was performed by seven acupuncturists with Masters or Doctorate degrees in Traditional Chinese Medicine (TCM), a California board certification, and at least 5 years of clinical experience.

Acupuncturists came to the patient's bedside within 3 h of enrollment, and they confirmed the patient's interest in acupuncture treatment and that the patient was currently experiencing pain and/or nausea. They then administered the pretreatment patient survey. Participants experiencing pain were asked questions on the location, type, characteristic, and severity of pain on both 10-point numerical and visual analogue scales. Participants experiencing nausea were asked questions according to the Rhodes Index, an eight-point validated tool that measures the patient's perception of nausea and vomiting.¹⁷

After the pretreatment survey, the acupuncturists collected TCM diagnostic information. The diagnostic evaluation began with a subjective review of standard questions (classically known as the “Ten Questions”) used in Chinese medicine, including the patients' perception of body temperature, sweat, sleep, energy, memory and/or concentration, appetite/digestion, thirst, urination, bowel movements, mood, and, if appropriate, menstruation. After this, the acupuncturist palpated the radial artery of each wrist, and visually examined the tongue. In addition, the acupuncturist noted the patient's blood pressure, heart rate, and performed a general physical exam.

After completing the diagnostic evaluation, acupuncturists identified the excess and/or deficient TCM pathologies observed in the patient. Excess pathologies chosen because of their association with pain and nausea included damp, damp heat, stomach qi rebellion, and qi and blood stagnation. Deficient pathologies also seen with these symptoms included yin deficiency, yang deficiency, qi deficiency, and blood deficiency. The acupuncturists were also encouraged to document any additional TCM diagnostic patterns observed.

After the diagnosis, acupuncturists administered needles to eight predetermined point locations to a standard needling depth for both pain and nausea. The acupuncture protocol and procedures employed adhered to the Standards for Reporting of Controlled Trials in Acupuncture (STRICTA) recommendations.¹⁸ Four points were chosen on the body and four in the ear for their known salutary effects on pain and nausea.^{11,16,19

–22} The points chosen for this study included LI4, LIV3, P6, and ST36 on the most accessible extremity, and Shenmen, Sympathetic, Stomach, and Thalamus on the most accessible ear (Fig. 2). Many ICU patients did not have both sides of the body accessible because of intravenous lines, pulse oximetry, etc. The depth of insertion for each point followed the Peter Deadman's protocol for acupuncture treatment.²³ The patients were all in the supine position to maximize accessibility of the needling points.

FIG. 2.

Point locations.

SEIRIN J Type .16 mm × 30 mm (40 gauge, 1 inch) single-use needles were used for the auricular points, and SEIRIN J type .20 mm × 30 mm (36 gauge, 1 inch) were used for the body points. Guide tubes were used to reduce variation between acupuncturists. Needles were inserted until a manual “De Qi” sensation was obtained by the acupuncturist. “De Qi” is experienced by patients as a numbness, tingling, fullness, or pressure at the point of insertion, and by acupuncturists as “needle grasping,” described as a tense, tight, and full sensation emanating through the needle.²⁴

The eight needles were retained for 20 min while the patient rested; any needles that fell out during this period were discarded and not reinserted. After removal of the needles and a needle count, the acupuncturist left the patient's bedside, and alerted the primary nurse. The nurse, unaware of the presurvey results, then administered a follow-up survey within 5 min of treatment, in which patients reported their pain level, subjective experience with the treatment, and distress caused by nausea according to the five-point grading scale within the Rhodes Index. Any adverse effects were also documented during this survey. Finally, the nurse documented pulse and blood pressure after treatment.

Patients received 3 days of treatment if they remained eligible on subsequent days. Ongoing pain or nausea was not a requirement for continued enrollment. On completion of the last treatment session, the patients were asked to complete a final survey on their overall experience of acupuncture, any additional effects noted, and whether they would recommend the treatment to other hospitalized patients.

In its entirety, the protocol took about 30–45 min to complete for each session.

Characteristics of patients, including age, gender, race/ethnicity, APACHE IVa scores with predicted mortality, predicted ICU length of stay (LOS), predicted hospital LOS, and reason for ICU admission, were collected (Table 2). The nurses' evaluations of the patients' pain, the timing and quantity of analgesic, and anti-emetic medications that the patients received both before and after acupuncture treatments were recorded. All opiate doses were converted to oral morphine equivalents.^25,26 Data were collected from the Medication Administration Records. Continuous infusions and long-acting medication were converted to hourly morphine equivalents. No patient received nonsteroidal anti-inflammatory drugs, and acetaminophen was not included.

Outcomes

The primary outcomes assessed were the proportion of patients eligible for acupuncture, the number who completed it, their perceptions of the effects of acupuncture treatment on pain and nausea, and the incidence of adverse effects related to acupuncture. Secondary outcomes included heart rate and blood pressure both before and after acupuncture, medication use, ICU and hospital LOS, and frequency and pattern of TCM diagnosis.

Statistical analysis

For statistical analysis, we compared pain and nausea scores before and after acupuncture by using a Wilcoxon Signed-Rank Test and repeated-measures test. All other variables were assessed by using descriptive statistics. The study group was compared with the rest of the ICU patients by using a simple t-test (Table 2). To test the effect of the acupuncture intervention on morphine dosage, we first conducted a descriptive analysis of the morphine equivalent doses. Variables were tested for normality before the application of a general linear model repeated test measure statistic with four factors. F statistics were used to compare mean morphine equivalent dose from pre- to postintervention with an underlying hypothesis that there was no difference in means from pre- to post-test (H₀ = Mean morphine dose_{preintervention} = Mean morphine dose_{post 1st-intervention} = Mean morphine dose_{post 2nd-intervention} = Mean morphine dose_{post 3rd-intervention}). The baseline preintervention morphine dose at 4 h was then compared with the postintervention morphine equivalent dose at 4 h after each of the three interventions on days 1 to 3.

Results

The results of patient recruitment are presented in Figure 3. During the study period, 530 patients were admitted to the ICU. Of these, 171 (32.2%) were referred to the RAs by the registered nurses as eligible candidates for acupuncture. Nine patients were transferred from the ICU before the RA interview. Of the remaining 162 patients, 68 (41.9%) consented to participate and were enrolled; of these, 22 (32.5%) were ineligible, declined treatment after enrollment, or were transferred out of the ICU before receiving acupuncture (Fig. 3). Reasons offered by patients for declining participation were noted by RAs, and they are summarized in Table 1. Table 2 compares acupuncture patients with all ICU patients. The study group was significantly younger, had a lower apache score and lower predicted mortality, and actual mortality as would be expected while considering the criteria with patients needing to be awake, alert, and consented.

FIG. 3.

Results of patient recruitment. P/N, pain/nausea; RNs, registered nurses; RAs, research assistants.

Table 1.

Reasons for Declining Treatment

	Total number	Percent of all referred patients
Not interested	35	21
Moved from ICU	28	17
Ineligible	28	17
Negative connotation with acupuncture	13	8
Fatigue	9	6
Fear of needles	9	6
Family preference	8	5
Feeling unwell	5	3

ICU, intensive care unit.

Table 2.

Comparison of ICU Study Participants Versus ICU Nonstudy Groups

	ICU (n = 46)	Non-ICU(n = 530)
Variable	n (%) or mean ± std	n (%)or mean ± std	Sig.
Age	47.40 ± 16.72	54.80 ± 19.35	0.006^a
Gender			0.172
Male	35 (76.1)	351 (66.2)
Female	11 (23.9)	179 (33.8)
Race/ethnicity			0.006
Black African	14 (30.4)	216 (40.8)
White/Caucasian	13 (28.3)	204 (38.5)
Other^b	19 (41.3)	110 (20.7)
Admitting service	24 (52.2)	335 (63.2)	0.411
Medicine	2 (4.4)	28 (5.3)
Neurosurgery	6 (13.0)	45 (8.5)
Surgery	14 (30.4)	122 (23.0)
Trauma
APACHE IV score	45.72 ± 20.11	56.65 ± 31.59	0.021
ICU LOS	4.42 ± 4.26	4.62 ± 5.96	0.828
Hospital LOS	11.75 ± 12.14	10.91 ± 12.67	0.66

Based on an independent sample t test.

Other included: American Indian/Alaska Native, Asian/Pacific Islander, Latin/Hispanic, and Other race/ethnicity.

LOS, length of stay.

Ultimately, 46 patients (67% of consented participants, 8.7% of all patients) received at least 1 day of acupuncture (Fig. 4). Altogether, 114 treatments were given: 45 of the 46 patients completed a post-treatment survey on day 1, whereas all patients completed a post-treatment survey on subsequent days.

FIG. 4.

Number of patients to receive acupuncture treatment by day. AMS, altered mental status.

Treatment effects

Patient perceptions of the effects of acupuncture treatment are detailed in Figure 5. The average self-reported pain level immediately after treatment decreased from the pain score reported immediately before treatment by 2.56 points on day 1, 2.36 points on day 2, and 1.98 points on day 3, p < 0.05. A repeated-measures test comparing the variance in pain pre- and postacupuncture over all 3 days showed a mean decrease of 2.36, p < 0.05. On day 1, 30 out of 46 patients (65%) reported a decrease in more than 1.5 points; on day 2, 21 out of 38 patients (55%) reported a decrease in more than 1.5 points; and on day 3, 17 out of 30 patients (57%) reported a decrease in more than 1.5 points.

FIG. 5.

Patient perceptions of the effects of acupuncture by day (A). Mean pain score both before and after acupuncture (B). Mean nausea score both before and after acupuncture.

Of the patients with nausea, the mean self-reported distress score decreased by 1.33 points on day 1, not at all on day 2, and by 0.82 points on day 3, which was not statistically significant. There were not enough patients who received anti-emetic medications to undergo analysis.

Mean morphine dosage before acupuncture treatment and 4 h after each treatment is shown in Figure 6. There was a significant decrease in morphine usage after each time point.

FIG. 6.

Mean morphine dosage preacupuncture treatment and 4 h after each treatment. Treatment effect at 4 h postintervention.

Over the course of three acupuncture treatments, there was a progressive increase in the percentage of patients reporting an overall benefit of acupuncture (Fig. 7). In response to the final survey regarding the patient's subjective experience of the treatment, the majority responded that acupuncture helped with pain and nausea (77%), and that they would recommend acupuncture to other hospitalized patients (84%). Some patients found that the therapy helped with other symptoms, in addition to pain and nausea (61%), most commonly an anxiolytic effect (79%), which has been previously reported.²⁷

FIG. 7.

Patients reporting benefits over 3 days of acupuncture.

No major adverse effects were reported. Two patients reported side-effects on the first day of acupuncture; the first experienced “a little pain,” with the insertion of the needle, whereas the second became agitated during the treatment and removed the needles after ∼10 min. The latter patient ultimately was not able to answer the follow-up survey due to agitation. A third patient reported worsening nausea on the second day of treatment, and so requested to be withdrawn from the study. No physicians declined participation of their patients in this study.

Over all 3 days of acupuncture treatment, acupuncturists inserted 909 needles, of which 16 fell out during treatment. The TCM diagnoses for treated patients are described in Table 3. The most common single diagnosis for pain was qi and blood stagnation (85%) followed by qi deficiency (53%), followed by yin deficiency (39%), though most patients had multiple TCM diagnoses identified. Qi and blood stagnation are commonly associated with pain. Stomach qi rebellion, often associated with nausea, was only seen in 3% of patients over the 3-day treatment.

Table 3.

Traditional Chinese Medicine Diagnoses for Treated Patients

	Day 1	Day 2	Day 3
	n (%)	n (%)	n (%)
Deficiency patterns
Yin	17 (37)	13 (34)	14 (47)
Yang	7 (15)	6 (16)	2 (7)
Blood	11 (24)	8 (21)	9 (30)
Qi	20 (43)	21 (55)	18 (60)
Other differentials Spleen Qi deficiency; Liv/Ht/Kd Yin deficiency; organ Yang deficiency	18 (39)	11 (29)	14 (47)
Excess patterns
Damp	5 (11)	6 (16)	6 (20)
Damp heat	10 (22)	7 (18)	8 (27)
Stomach heat/stomach Qi rebellion^a	6 (13)	4 (11)	5 (17)
Qi and blood stagnation^b	39 (85)	31 (82)	26 (87)
Other differentials: liver Qi stagnation; damp heat in Jiaos; dampness in organs/Jiaos; phlegm Stasis	43 (93)	8 (21)	6 (20)

Associated with nausea.

Associated with pain.

Finally, vital signs both before and after acupuncture were analyzed. Heart rate was seen to decrease by 1.93 beats per min, systolic blood pressure was found to decrease by 2.4 mmHg, and diastolic blood pressure was seen to decrease by 1.1 mmHg, none of which was significant.

Limitations

This study was intended to assess the feasibility of acupuncture therapy within an ICU, and it was not designed to establish the efficacy of acupuncture for pain or nausea relief. There was no control group, sham procedure, randomization, or blinding process, and the study involved a small sample size (n = 46) in a single center.

Most ICU patients improve spontaneously over time, as did our patients from day 1 to 3 (Fig. 5a). Although the decrease in pain during the study period could reflect this natural progression of healing, the fact that patients had an immediate self-reported benefit and lower morphine requirements 4 h post-treatment suggests that acupuncture may have had an independent effect.

Patients in the acupuncture group received at least 45 min each day of extra care, including answering questions and receiving treatments. Although it is possible that this extra attention contributed to a reduction of pain and opiate medication, it is difficult to assess the effect in a nonblinded study.

Classically, acupuncturists individualize therapy to address the pattern of pathologies observed from the complete Chinese medicine diagnosis. For the sake of standardization, we limited the number of points to eight, and we did not individualize further. From a TCM point of view, this could potentially reduce the effectiveness of treatment.

Discussion and Conclusion

This study demonstrated that ICU patients are receptive to acupuncture treatment, and that such treatment may alleviate pain. Although there was no significant reduction in the Rhodes Index of nausea during the study, about half of the patients reported an improvement in nausea after treatment.

The nurses deemed that approximately one-third of the patients admitted to the ICU were eligible for recruitment and of these, 42% consented to participation. This enrollment rate is similar to that found in the only other U.S. study of acupuncture in an adult ICU, where 41% of patients accepted acupuncture treatment.¹⁶ Both acceptance rates are higher than the 20% or less enrollment rates typically seen in clinical trials of ICU patients.^28,29 Of the patients who declined, only 14% did so due to negative connotations with acupuncture or fear of needles. Although the overall use of acupuncture in the ICU was low, 8% of all patients in the ICU during the study period, our inclusion criteria were strict, our patients had a higher acuity than average ICU patients (APACHE IVa 56.9 vs. national average APACHE IVa 50), and the lack of adverse effects and the potential decrease in opiate use make acupuncture an attractive treatment modality.

Over the enrollment period, 114 treatments were completed in 46 patients, compared with 64 treatments in 20 patients in the study by Yeh et al.. Our study completion rates and the reason for missing treatment days were similar to those found by Yeh et al. Effects were minimal in both studies, and no obstacles were identified that might limit acupuncture treatment in the ICU. These results are consistent with previous research on adverse effects associated with acupuncture, which tend to be minor (bruising, nausea) and extremely infrequent (1/1,000 treatments).³⁰

According to the National Center for Health Statistics, most recipients of acupuncture tended to be women, Asian, highly educated, and patients with private insurance.^31,32 In contrast, our patients were predominantly men (76%), non-Asian (89%), and having achieved a high school education or less (50%). In addition, the majority of patients were acupuncture naïve (68%) and only 26% were privately insured.

Patients who received acupuncture had a lower acuity (initial APACHE IVa score of 45.7) than the rest of the ICU patients (initial APACHE IVa score of 56.9) but were close to the national average ICU admission score of 50. ICU and hospital LOS were similar in both groups.

The decrease in pain scores achieved by acupuncture in our study is similar to that seen in acupuncture studies in other settings.³⁰ The mean decrease in pain observed, 2.39, is above the commonly accepted threshold for clinically relevant analgesia.³³ Although not an endpoint in our study, nearly half (49%) of all the participants spontaneously reported an anxiolytic effect from acupuncture. A strong association between anxiety and pain has been demonstrated in a variety of conditions.³⁴ Moreover, anxiety has been described as limiting future quality of life after ICU admission.⁵

In conclusion, this study demonstrates that acupuncture is feasible, 32% of ICU patients were deemed eligible by ICU RNs, safe, with no major adverse effects, and acceptable, and almost 9% of all ICU patients completed at least one treatment. The low overall number of patients treated suggests that acupuncture may not be practical as a stand-alone adjunctive therapy in the ICU, but could easily be incorporated into hospitals such as ours with a comprehensive acupuncture service. Participating patients reported improvement in their symptoms and an overall beneficial effect. These results warrant a larger, randomized, prospective trial on acupuncture in the ICU.

Footnotes

Acknowledgments

The authors would like to thank: Alex Feng, Jamie Hampton, Wayne Matecki, Chris Randle, Ky Yu, Anuj Ohri, Irene Yen, Miranda Weintraub, Hansen Deng, Lisa Lim, Chizobam Ani, Linne Almer, James Feeney, Colleen Callahan, and Laurie Bagley.

Author Disclosure Statement

All authors have no competing financial interests. Dr. Feeney and Dr. Matecki are on the Board of Directors of the California nonprofit corporation International Center for Integrative Medicine.

References

Joffe

, Hallman

, Gélinas

, et al. Evaluation and treatment of pain in critically ill adults. Semin Respir Crit Care Med, 2013; 34:189–200.

Collins

. Postoperative nausea and vomiting in adults: Implications for critical care. Crit Care Nurse, 2011; 31:36–45.

Makic

MBF

. Management of nausea, vomiting, and diarrhea during critical illness. AACN Adv Crit Care, 2011; 22:265–274.

Barr

, Fraser

, Puntillo

, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med, 2013; 41:263–306.

Schug

, Palmer

, Scott

, et al. Acute pain management: Scientific evidence, fourth edition, 2015: 2016; 204:315–317.

Lizana

, Bota

, De Cubber

, Vincent

J-L

. Long-term outcome in ICU patients: Intensive Care Med, 2003; 29:1286–1293.

Dowling

. Autonomic measures and behavioral indices of pain sensitivity. Pain, 1983; 16:193–200.

Skrobik

, Ahern

, Leblanc

, et al. Protocolized intensive care unit management of analgesia, sedation, and delirium improves analgesia and subsyndromal delirium rates. Anesth Analg, 2010; 111:451–463.

Takahashi

. Acupuncture for functional gastrointestinal disorders. J Gastroenterol, 2006; 41:408–417.

10.

Hui

KKS

, Marina

, Liu

, et al. Acupuncture, the limbic system, and the anticorrelated networks of the brain. Auton Neurosci, 2010; 157:81–90.

11.

Lee

, Chan

SKC

, Fan

LTY

. Stimulation of the wrist acupuncture point PC6 for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev, 2015:CD003281.

12.

Gan

, Diemunsch

, Habib

, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg, 2014; 118:85–113.

13.

Pfab

, Winhard

, Nowak-Machen

, et al. Acupuncture in critically ill patients improves delayed gastric emptying: A randomized controlled trial. Anesth Analg, 2011; 112:150–155.

14.

Chernyak

, Sessler

. Perioperative acupuncture and related techniques. Anesthesiology, 2005; 102:1031–1049; quiz 1077–1078.

15.

Chen

, Houghton

, Seefeld

, et al. A survey of selected physician views on acupuncture in pain managementpme. Pain Med, 2010; 11:530–534.

16.

Yeh

, Mirocha

, Brantman

, et al. A preliminary investigation on the acceptance and feasibility of acupuncture in the intensive care unit. ICU Dir, 2013; 4:82–87.

17.

Rhodes

, Watson

, Johnson

. Development of reliable and valid measures of nausea and vomiting. Cancer Nurs, 1984; 7:33–41.

18.

MacPherson

, White

, Cummings

, et al. Standards for reporting interventions in controlled trials of acupuncture: The STRICTA recommendations. J Altern Complement Med, 2002; 8:85–89.

19.

Grissa

, Baccouche

, Boubaker

, et al. Acupuncture vs intravenous morphine in the management of acute pain in the ED. Am J Emerg Med, 2016; 34:2112–2116.

20.

Maciocia

. The Foundations of Chinese Medicine: A Comprehensive Text for Acupuncturists and Herbalists, 2nd edition. Edinburgh; Churchill Livingstone, 2005.

21.

Maciocia

. The Practice of Chinese Medicine: The Treatment of Diseases with Acupuncture and Chinese Herbs, 2nd edition. Edinburgh; Churchill Livingstone, 2007.

22.

Xinnong

, et al. Chinese Acupuncture and Moxibustion. Beijing: Foreign Languages Press, 1987.

23.

Deadman

, Baker

, Al-Khafaji

. A Manual of Acupuncture: Journal of Chinese Medicine Publications. Ann Arbor, MI: Cushing Mallory, 2001.

24.

Yang

X-Y

, Shi

G-X

, Li

Q-Q

, et al. Characterization of deqi sensation and acupuncture effect. Evid Based Complement Alternat Med, 2013:319734.

25.

Brunton

, Chabner

, Knollman

. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 12th edition. New York: McGraw Hill Professional, 2011.

26.

Ohri

. Pharmacotherapy Principles & Practice. Chisholm-Burns

, Wells

, Schwinghammer

, Malone

, Kolesar

, Rotschafer

, DiPiro

. New York, NY: Published by The McGraw-Hill Companies, Inc., 2008. ISBN 978-0-07-148934-8. 2008; 42:730–730.

27.

Zheng

, Meng

J-B

, Fang

. Electroacupuncture reduces the dose of midazolam monitored by the bispectral index in critically ill patients with mechanical ventilation: An exploratory study. Acupunct Med, 2012; 30:78–84.

28.

Meduri

, Golden

, Freire

, et al. Methylprednisolone infusion in early severe ARDS: Results of a randomized controlled trial. Chest, 2007; 131:954–963.

29.

Girard

, Kress

, Fuchs

, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): A randomised controlled trial. Lancet, 371:126–134.

30.

MacPherson

, Thomas

, Walters

, Fitter

. A prospective survey of adverse events and treatment reactions following 34,000 consultations with professional acupuncturists. Acupunct Med, 2001; 19:93–102.

31.

Barnes

. Complementary and Alternative Medicine Use Among Adults: U.S. 2002. Darby, PA: DIANE Publishing, 2009.

32.

Vickers

, Cronin

, Maschino

, et al. Acupuncture for chronic pain: Individual patient data meta-analysis. Arch Intern Med, 2012; 172:1444–1453.

33.

Ruyssen-Witrand

, Tubach

, Ravaud

. Systematic review reveals heterogeneity in definition of a clinically relevant difference in pain. J Clin Epidemiol, 2011; 64:463–470.

34.

McWilliams

, Goodwin

, Cox

. Depression and anxiety associated with three pain conditions: Results from a nationally representative sample. Pain, 2004; 111:77–83.