This research paper evaluated the effects of acupuncture at point Pericardium 6 (PC6) on nausea and vomiting induced by hydromorphone administration in healthy dogs. 81 dogs were randomly assigned to receive acupuncture at PC6, alternative acupuncture at Lung 5, or no acupuncture. After hydromorphone injection, dogs that received acupuncture at PC6 had a significantly lower incidence of vomiting compared to the other groups. Acupuncture at PC6 reduced vomiting in dogs but did not affect other signs of nausea like hypersalivation or licking. The study suggests acupuncture at PC6 can decrease opioid-induced vomiting in dogs during the perioperative period.

1. RESEARCH PAPER
The effects of acupuncture point Pericardium 6 on
hydromorphone-induced nausea and vomiting in healthy
dogs
Elizabeth M Scallan & Bradley T Simon
Department of Clinical Sciences, School of Veterinary Medicine, Ross University, Basseterre, St Kitts, West Indies
Correspondence: Bradley T Simon, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences,
Texas A&M University, 402 Raymond Stotzer Parkway, College Station, TX 77845, USA. E-mail: Bsimon@cvm.tamu.edu
Present address: Elizabeth M Scallan, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical
Sciences,Texas A&M University, College Station, TX, USA
Abstract
Objective To evaluate the effect of needling at
acupuncture point Pericardium 6 on hydromor-
phone-induced nausea and vomiting.
Study design Randomized controlled clinical study.
Animals Eighty-one mixed-breed, healthy dogs
aged 1.8 Æ 1.6 years and weighing 14.5 Æ 5.6
kg, admitted for elective ovariohysterectomy (n =
75) or castration (n = 6).
Methods Dogs were randomly assigned to one of
three groups: acupuncture at Pericardium 6 (AT, n =
27); alternative acupuncture at Lung 5 (ST, n = 27),
and no acupuncture (CT, n = 27). During time 0–30
minutes (baseline), occurrences of hypersalivation,
vomiting and licking were recorded. At 30 minutes,
subjects were administered hydromorphone (0.1 mg
kgÀ1
) in combination with acepromazine (0.03 mg
kgÀ1
) intramuscularly. During time 30–45 minutes
(post-injection), occurrences of hypersalivation, vom-
iting and licking were recorded by an observer
unawareofgroupassignment.Groupswerecompared
using a Kruskal–Wallis test followed by a Dunn’s post-
test, or Fisher’s exact tests when appropriate.
Results There were no significant differences in age,
weight or baseline observations among groups.
Vomiting incidence post-injection was higher in
the CT (20/27, 74.1%) and ST (22/27, 81.5%)
groups than in the AT (10/27, 37.0%) group
(p = 0.0129 and p = 0.002, respectively). The num-
ber of vomiting episodes [median (range)] after opioid
administration was higher in the ST [1 (1–6)]
than the AT [0 (0–2)] group (p = 0.0040). There
were no differences in the median number of vom-
iting episodes between the ST and CT [1 (0–3)] or AT
and CT groups. There were no differences in hyper-
salivation or licking among groups after hydromor-
phone–acepromazine administration.
Conclusions and clinical relevance Pericardium 6
acupuncture reduced the incidence of hydromor-
phone-induced vomiting in healthy dogs. This cost-
effective technique can improve patient well-being
and comfort during the perioperative period.
Keywords acupuncture, dog, hydromorphone,
opioid, vomiting.
Introduction
Acupuncture is the art of stimulating specific and
previously defined loci. The classic acupuncture point
is a locus located beneath the skin that reaches the
surface and is formed of a neurovascular and
lymphatic bundle encompassed by a sheath of con-
nective tissue (Mittleman & Gaynor 2000). Acupunc-
ture points orloci may also lie along meridians, which
can follow major nerve, vessel and fascial cleavage
planes (Mittleman & Gaynor 2000). Perioperative
acupuncture has been effective in enhancing seda-
tion, in the treatment of acute and chronic pain, and
in decreasing systemic opioid use, minimizing car-
diovascular complications, and managing postoper-
ative nausea and vomiting (Kotani et al. 2001;
Chernyak & Sessler 2005; Streitberger et al. 2006;
Hayashi et al. 2007; Gakiya et al. 2011; Schliess-
495
Veterinary Anaesthesia and Analgesia, 2016, 43, 495–501 doi:10.1111/vaa.12347

2. bach et al. 2011; Vickers et al. 2012; Cheong et al.
2013; Lee et al. 2013; Fry et al. 2014).
Acupuncture point Pericardium 6 (PC6) has been
used in humans and dogs to treat and prevent
nausea and vomiting and is considered the most
effective anti-emetic point (Streitberger et al. 2006;
Hosbach 2008; Lee et al. 2013; Alizadeh et al.
2014; Koh et al. 2014). The anti-emetic effect of
acupuncture can be an important part of anesthetic
management as vomiting can lead to aspiration
pneumonia, increased intra-abdominal and thoracic
pressure, arterial hypertension, increases in intra-
cranial pressure and patient discomfort (Eberhart
et al. 2007; Tart et al. 2010).
Acupuncture point Lung 5 (LU5) follows the lung
meridian and is termed Chi Ze (Hwang & Limehouse
2001). It is indicated for use in canine patients with
elbow pain, paralysis of the distal thoracic limb and
respiratory disorders (Hwang & Limehouse 2001). In
humans, points along the lung meridian were shown
to affect heart rate, body temperature, consciousness,
asthma and laryngospasm, but to have no effect on
vomiting or nausea (Hosbach 2008).
Opioids such as hydromorphone are commonly
used perioperative analgesics in small animal anes-
thetic protocols and have an analgesic mechanism of
action mainly as agonists on l-opiate receptors at
both the spinal and supraspinal levels (Schafer
2011). A disadvantage associated with the intra-
muscular (IM) administration of these opioids in
healthy dogs is vomiting and nausea (Valverde et al.
2004; Wilson et al. 2005; Johnson 2013).
The primary objective of this study was to
determine if single-point acupuncture at PC6 affects
occurrences of hypersalivation, self-licking and
vomiting in healthy dogs administered hydromor-
phone and acepromazine for elective procedures.
The primary hypothesis was that acupuncture at
PC6 will reduce the occurrence of hypersalivation,
licking and vomiting in these patients. The
secondary objective was to determine if acupuncture
at LU5 has significant effects on opioid-induced
nausea and vomiting in comparison with no
acupuncture therapy. The secondary hypothesis
was that acupuncture at LU5 will have no effect
on opioid-induced nausea and vomiting.
Materials and methods
All aspects of this research were approved by the Ross
University School of Veterinary Medicine (RUSVM)
Institutional Animal Care and Use Committee. Own-
ers provided written consent for the participation of
the dogs enrolled in this study but were not aware of
which treatment (acupuncture, sham or control)
would be administered to their animals.
The study population consisted of 81 healthy,
mixed-breed dogs assigned American Society of
Anesthesiologists (ASA) class I status presenting to
the RUSVM community practice for elective surgical
procedures. Physical status was determined by
history, physical examination, complete blood count,
total protein, blood urea nitrogen and serum glucose.
The study population consisted of 75 females and six
males undergoing ovariohysterectomy and castra-
tion, respectively. Mean Æ standard deviation (SD)
age and weight were 1.8 Æ 1.6 years and 14.5 Æ
5.6 kg, respectively. Patients were fasted for
12 hours prior to the procedure. Water was available
ad libitum until the morning of the procedure.
According to a prospective, randomized, con-
trolled study design, the 81 dogs were randomly
assigned using computer software (www.random-
izer.org) to one of three treatment groups: group AT,
acupuncture at PC6 (n = 27); group ST, alternative
acupuncture at LU5 (n = 27), and group CT, control
or no acupuncture (CT, n = 27).
Baseline measurements and experiment protocol
Each patient was placed in a quiet isolated room
for observations. Patients in AT were administered
acupuncture by a certified veterinary acupunctur-
ist (EMS) at point PC6 on both thoracic limbs. PC6
(Nei Guan) is located within the muscular groove at
about one-sixth of the distance from the carpus to
the cubital fossa between the flexor carpi radialis
and superficial digital flexor muscle intersection
with the corresponding tendons (Hwang & Lime-
house 2001). Acupuncture point PC6 was identi-
fied by palpation of the defined anatomical
landmarks. Patients in ST were administered
acupuncture by the same acupuncturist on both
thoracic limbs at point LU5 (Chi Ze) located on the
cubital fossa of the thoracic limb, in a depression
lateral to the biceps brachii tendon and medial to
the extensor carpi radialis (Hwang & Limehouse
2001). Acupuncture point LU5 was also located by
palpation of the defined anatomical landmarks.
Patients in CT were not administered acupuncture
stimulation.
Acupuncture needle selection was based on the
size of the patient. The needles used in this study
included needles measuring 0.18 9 15 mm and
496 © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 495–501
PC6 in hydromorphone-induced vomiting EM Scallan and BT Simon

3. 0.16 9 15 mm (Seirin America, Inc., MA, USA),
and needles measuring 0.2 9 13 mm and
0.3 9 13 mm (Kingli Medical Appliance Co. Ltd,
Jiangsu, China). After the needles had been placed,
baseline observations commenced for 30 minutes
(T = 0–30 minutes) for all groups. During this
time, vomiting episodes, licking of the muzzle and
the occurrence of hypersalivation were recorded.
The observers were seven second- and third-year
veterinary students with no prior acupuncture
training, who were unfamiliar with the specific
locations of acupuncture therapy points PC6 and
LU5, and were asked to avoid gathering knowl-
edge on acupuncture point location and target
uses during the study. Therefore, the observers
were considered to be unaware of treatment
allocation. Each patient was observed by the same
single student throughout the study (45 minutes).
The acupuncture needles remained in place and
were visible to the observers.
At the end of baseline recording (T = 30 min-
utes), each patient was administered an injection of
hydromorphone (0.1 mg kgÀ1
; hydromorphone
hydrochloride injection, USP, 2 mg mLÀ1
; West-
Ward Pharmaceutical Corp., NJ, USA) and acepro-
mazine (0.03 mg kgÀ1
; acepromazine maleate, 10
mg mLÀ1
; Vedco, Inc., MO, USA) into the lumbar
epaxial muscles.
Post-injection measurements
Each patient was observed by the same observer in
the same room for 15 minutes (T = 30–45 min-
utes) after drug administration. Vomiting episodes,
number of licks and presence of hypersalivation were
recorded for each patient. If an acupuncture needle
was dislodged, the acupuncturist replaced the needle
immediately. The patient was transferred to the
anesthesia service at T = 45 minutes for the sched-
uled elective surgical procedure.
Each patient was assigned to one of five categories
for statistical analysis based on the number of licks
observed: category 0, no licks; category 1, one to 30
licks; category 2, 31–50 licks; category 3, 51–70
licks, and category 4, >70 licks.
Statistical analysis
Statistical analysis was performed using GraphPad
Prism Version 6.07 (GraphPad Software, Inc., CA,
USA). Age, vomiting episodes and licking categories
were analyzed using Kruskal–Wallis tests followed by
Dunn’s post-tests for multiple comparisons.Sex,hyper-
salivation and vomiting incidences were analyzed
using Fisher’s exact tests. Patient weight was analyzed
using one-way analysis of variance (ANOVA). Results
were reported as the median (range) or mean Æ SD as
appropriate. Incidences of vomiting and hypersaliva-
tion were also reported as percentages. A power
analysis revealed that 27 dogs per group (n = 81)
would be sufficient to detect a clinically relevant
difference (of ≥35%) in the incidence of vomiting in
order to obtain a power of 80% (0.80) with a
significance level of a = 0.05. A p-value of <0.05 was
consideredtoindicatestatistical significancefor alldata
analyzed.
Results
Patient distribution
There were no statistical differences among the
groups in age, weight or sex. Mean Æ SD age by
group was 1.7 Æ 1.5 years in AT, 2.0 Æ 2.1 years
in ST and 1.8 Æ 1.1 years in CT. Mean Æ SD
patient weight was 13.7 Æ 6.1 kg in AT,
14.6 Æ 5.6 kg in ST and 15.5 Æ 5.0 kg in CT.
There were two, three and one male(s) in the AT, ST
and CT groups, respectively; all remaining dogs were
female.
Baseline
No dogs vomited during the baseline period. Hyper-
salivation was observed in one dog in AT and one
dog in CT. Median (range) licking categories in AT,
ST and CT prior to premedication were 1 (0–4), 1 (0–
2) and 1 (0–3), respectively; differences were not
statistically significant. The numbers of dogs licking
their muzzles prior to premedication in AT, ST and
CT were 19 of 27 (70.4%), 18 of 27 (66.7%) and 11
of 27 (40.7%), respectively.
Behavior after premedication
Significantly more dogs vomited in ST (22/27, 81.5%)
and CT (20/27, 74.1%) compared with AT (10/27,
37.0%) (p = 0.002 and p = 0.0129, respectively)
(Fig. 1a). The median (range) number of vomiting
episodesindogsthatvomitedwere0(0–2)inAT,1(0–
6) in ST, and 1 (0–3) in CT; the frequency of vomiting
was significantly higher in ST than in AT (p = 0.004)
(Fig. 1b). There were no differences in vomiting
frequencies between ST and CT or AT and CT.
497© 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 495–501
PC6 in hydromorphone-induced vomiting EM Scallan and BT Simon

4. Licking and hypersalivation post-premedication
The numbers of dogs licking their muzzles post-
premedication in the AT, ST and CT groups were 26
(96.3%), 27 (100%) and 25 (92.6%), respectively.
The median (range) frequency of licking according
to numerical category was 2 (0–4) in AT, 2 (1–4) in
ST and 2 (0–4) in CT, and did not differ among the
groups (Fig. 1c). Hypersalivation was observed in
five of 27 (18.5%) dogs in AT, six of 27 (22.2%) dogs
in ST and 12 of 27 (44.4%) dogs in CT; there were no
differences among the groups (Fig. 1d).
Discussion
In this study, acupuncture at point PC6 signifi-
cantly inhibited vomiting, but not the clinical signs
associated with nausea (hypersalivation or licking)
after IM administration of hydromorphone. In
human medical practice, regardless of inpatient or
outpatient settings, perioperative nausea and vom-
iting have been reported to increase the cost of the
patient’s care by 10–215% (Kane-Gill et al. 2014).
It is thought that prevention rather than treatment
is the most desirable method of minimizing patient
costs associated with nausea and vomiting induced
by opioids (Kane-Gill et al. 2014). The aim of this
study was to provide the attending practitioner with
an alternative to traditional pharmaceutical ther-
apy for opioid-induced nausea and vomiting with
minimal cost and side effects.
Opioid-induced vomiting is attributed to stimula-
tion of the d-receptor within the chemoreceptor
trigger zone (CTZ) outside the blood–brain barrier
(Blancquaert et al. 1986). This area is a circumven-
tricular organ located on the floor of the fourth
Figure 1 1 (a) Incidence of vomiting, (b) vomiting frequency, (c) licking categories and (d) incidence of hypersalivation in
81 dogs during the 15 minutes after intramuscular administration of hydromorphone (0.1 mg kgÀ1
) and acepromazine
(0.03 mg kgÀ1
). At 30 minutes before drug administration, dogs were administered one of acupuncture at Pericardium 6
(AT), acupuncture at Lung 5 (ST), or no acupuncture (CT) (n = 27 dogs in each group). Boxplots indicate 25–75th
percentiles; whisker plots indicate minimum to maximum. Medians that differ from the 25th and 75th percentiles are
indicated by a horizontal bar between those values. *Significantly different from ST and CT (p = 0.0009 and p = 0.0129,
respectively). †Significantly different from ST (p = 0.004).
498 © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 495–501
PC6 in hydromorphone-induced vomiting EM Scallan and BT Simon

5. ventricle in the postrema medulla (Wang & Glaviano
1954; Costello & Borison 1977; Mitchelson 1992;
Takahashi et al. 2007). It is suggested that the lower
lipid solubility of hydromorphone results in an initial
stimulation of the d-receptors located in the CTZ
prior to inhibiting the vomiting center within the
medulla (Blancquaert et al. 1986). Therefore,
increasing the lipid solubility of the opioid decreases
the associated incidence of vomiting.
The effects of acupuncture on nausea and vom-
iting occurring postoperatively and induced by
chemotherapy, pregnancy and motion have been
evaluated in humans. It was concluded that
acupuncture at PC6 administered prior to emesis is
effective in reducing postoperative nausea and
vomiting, although there is less evidence to support
its use during pregnancy (Streitberger et al. 2006).
Koh et al. (2014) reported that electroacupunc-
ture minimized morphine-induced vomiting in dogs.
Acupuncture may be beneficial as an adjunct to
veterinary care, but training in the performance of
acupuncture and the purchase of equipment for
electroacupuncture require financial investment. In
the current study, a single acupuncture point was
used as a practical and cost-effective alternative to
electroacupuncture. Although this technique was
performed by a certified acupuncturist, the authors
believe that acupuncture at PC6 can easily be taught
to general practitioners to be used in everyday
practice, similar to the availability of the resuscita-
tion point GV 26.
The anti-emetic mechanism of PC6 was suggested
by Tatewaki et al. (2004) in a canine model
evaluating the effects of electroacupuncture on
vasopressin-induced vomiting in dogs. The authors
suggested that a central opioid pathway is involved
and that electrostimulation of PC6 releases endoge-
nous opioids from the central nervous system to
inhibit vomiting at the vomiting center (Tatewaki
et al. 2004). Based on this theory, PC6 stimulation
should play an active role against the peripheral
emetic effects of low lipid-soluble opioids in the CTZ.
In the current study, acupuncture at point PC6
was used to inhibit the vomiting effects of opioids.
The results of this study show a reduction in the
incidence of vomiting of up to 50% with the use of
PC6. In the present data, the incidences of vomiting
in dogs without acupuncture at PC6 (81.5% and
74.1%) were greater than those reported previously
after the administration of hydromorphone in the
same dosage range. Incidences of vomiting were
46% in dogs administered hydromorphone
(0.1 mg kgÀ1
) and acepromazine (0.03 mg kgÀ1
)
IM (Johnson 2013) and 50% in dogs administered
hydromorphone (0.1 mg kgÀ1
) and acepromazine
(0.05 mg kgÀ1
) IM (Valverde et al. 2004). Admin-
istration of hydromorphone IM alone induced vom-
iting in 25% of dogs at 0.1 mg kgÀ1
(Hay Kraus
2014) and in 87% of dogs at 0.2 mg kgÀ1
(Claude
et al. 2014). Thus, the presence of vomiting after
hydromorphone administration seems to vary with
study conditions, duration and presence of fasting,
between client-owned and research-bred animal
populations, and according to the dose and route
of the hydromorphone, and concurrent administra-
tion of other medications (Hay Kraus 2014).
Vomiting episodes in dogs in which acupuncture
point PC6 was used were reduced in comparison with
those in dogs in which acupuncture point LU5 was
used. No significant differences in the number of
vomiting episodes were noted when PC6 acupunc-
ture was compared with no acupuncture therapy.
Therefore, more studies are needed to verify if PC6
acupuncture is effective in reducing vomiting epi-
sodes in dogs after hydromorphone administration.
Acepromazine administered 15 minutes prior to
morphine and hydromorphone premedication
reduced the incidence of vomiting in dogs; however,
the simultaneous administration of an opioid and
acepromazine did not statistically decrease the
incidence of vomiting (Valverde et al. 2004). There-
fore, the use of acepromazine should not influence
the results in this study.
Nausea has been described as the first phase of
vomiting (Twedt 2005). Nausea in this study was
diagnosed based on the incidence of hypersalivation
and frequency of licking behaviors. The purpose of
these behaviors is to coat the esophagus in bicar-
bonate-rich saliva, minimizing esophageal damage
from acidic gastric reflux (Twedt 2005). The use of
single-point acupuncture at PC6 did not reduce the
incidence of nausea in this study. By contrast, Koh
et al. (2014) reported that signs of nausea were
significantly reduced during PC6 electroacupunc-
ture in comparison with sham (non-acupoint)
treatment. In a systematic review of six pooled trials,
acupuncture point PC6 reduced nausea in humans
in comparison with a sham control to an incidence
of 20.8% versus 43.4% (Cheong et al. 2013). Fur-
ther studies are recommended using single-point
acupuncture in dogs to determine its effects on
inhibiting nausea.
Retching is the second phase of vomiting and is
characterized by forceful abdominal and diaphrag-
499© 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 495–501
PC6 in hydromorphone-induced vomiting EM Scallan and BT Simon

6. matic contractions without expulsion of gastric
contents (Twedt 2005). Although retching was not
analyzed in this study, previously published studies
have included this evaluation (Valverde et al. 2004;
Koh et al. 2014). Further studies should be con-
ducted to evaluate the efficacy of acupuncture at
PC6 in inhibiting retching in dogs administered
hydromorphone.
The utilization of sham acupuncture points has
been controversial (He et al. 2013; Huang et al.
2013). A ‘sham point’ is defined as an ‘irrelevant
acupuncture point’ that provides results similar to
those in the control (Zhang et al. 2014). Sham
acupuncture has been described as the superficial
needling of similar points, needling of defined
acupuncture points that are irrelevant to the desired
effect, needling of non-defined acupuncture points,
the use of placebo needles, and pseudo-interventions
(Zhang et al. 2014). Sham acupuncture has been
noted to have potent placebo effects in humans and
may alter an individual’s psychological perception if
that person believes that any treatment with
acupuncture may work (Huang et al. 2013). Vickers
et al. (2012) describes this as altering patient per-
ception. Similarly, He et al. (2013) found inconsis-
tencies in controlled clinical trials that used sham
acupuncture. The authors of the present study
suggest that in dogs that have never received
acupuncture previously, the anticipation of an
expected effect is not conceptualized and therefore a
placebo effect is less likely to occur.
Acupuncture point LU5 was chosen because it is
not located along the same meridian as PC6 and has
not been reported to have any effects on gastroin-
testinal motility, nausea and vomiting, and because
its location in the general vicinity (distal thoracic
limb) of PC6 may deter point recognition by
observers. Given the lack of any significant differ-
ences between outcomes in groups ST and CT, the
present authors conclude that acupuncture point
LU5 does not have anti-emetic properties against
opioid-induced nausea and vomiting. Additional
studies utilizing LU5 are required to determine if
this point is an acceptable sham point as a control in
studies investigating opioid-induced nausea and
vomiting in dogs.
This study is limited by the fact that observers
were not blinded to the group status of dogs in the
control treatment because they were able to identify
when needles were not placed. Methods of preserv-
ing blinding may include videotaping the patient
from above the carpus so that video-recording can be
evaluated by the observer at a later date or,
alternatively, bandaging the thoracic limbs to cover
the presence or absence of acupuncture needles.
In conclusion, single-point acupuncture at PC6,
administered prior to hydromorphone IM premedica-
tion, significantly reduced the likelihood of vomiting
but not signs of nausea in healthy dogs. Acupuncture
at point LU5 does not reduce vomiting in healthy
dogs. Further studies are needed to validate LU5 as an
acceptable sham point for use in studies assessing
opioid-induced nausea and vomiting.
Acknowledgements
The authors would like to thank Jessica Campbell,
Anthony Fernandez, Amanda Maijer, Kelsey
McCann, Jillian VanderYacht, Leanne Wagener
and Aubrielle Williams (School of Veterinary Med-
icine, Ross University, St Kitts, West Indies), Dr Shari
Lanning (Department of Biomedical Sciences,
School of Veterinary Medicine, Ross University) and
Michaela Witcher (Department of Clinical Sciences,
School of Veterinary Medicine, Ross University).
Authors’ contributions
EMS and BTS contributed to the conception and
design of the study, the acquisition of data, and the
drafting and revision of the manuscript. BTS per-
formed the statistical analyses. Both authors
approved the final manuscript for publication.
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Received 29 August 2015; accepted 21 December 2015.
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PC6 in hydromorphone-induced vomiting EM Scallan and BT Simon