Postoperative Nausea and Vomiting: 168 Years in Review-Juniper Publishers
Juniper Publishers-Journal of Anesthesia
Abstract
DiLustro is the inventor of the multi-modal PONV 
Pressure Point therapy technique. Research and expanding use of this 
technique has proven to be a safe and effective multi-modal choice in 
PONV management. The company's acu-stimulation adhesive technique 
enhances anesthesiology benefits, such as, nausea and vomiting 
prophylaxis, elimination of expensive or risk-based rescue drug 
therapies and broader patient satisfaction, with no reported adverse 
effects. This evidence-based anesthetic-related technique provides an 
extended duration (72 hours) of PONV therapy to support Enhanced 
Recovery after Surgery (ERAS) protocol reimbursement practices. 
Introduction
The introduction of volatile agents such as ether and
 chloroform in the 1840s was heralded as the most important medical 
innovation. However, the phenomenon of postoperative nausea and vomiting
 (PONV) became evident within only two years, and remains as a major 
complication for general anesthesia today. The first report on the 
devastating effect of PONV was published in 1848 by Dr. John Snow, a 
British anesthesiology pioneer who described his findings on this 
disturbing complication associated with surgery and anesthesia. Until 
his untimely death in 1858 at the age of 45 years, Dr. Snow was one of 
the foremost authorities in the administration of anesthesia [1].
During the ether era of 1846 to 1950, the incidence of PONV was reported to be as high as 75-80% [2].
 During this time in an effort to reduce the incidence of PONV, 
neuroleptic drugs were considered the most efficacious pharmacotherapy 
because of the inherent anti-emetic properties of this drug class. The 
first prophylactic use of an anti-emetic drug derived from the 
neuroleptic phenothiazine drug class was introduced in the 1880s [2].
 Neuroleptic phenothiazine drugs block receptors in the central nervous 
system's (CNS) dopamine pathways which mitigate the effects of nausea.
The Emergence of Anti-Emetic Therapy
Almost half a century later, the use of new 
neuroleptic class of promethazine drugs emerged to further reduce the 
incidence of PONV [3].
 Promethazine pharmaceuticals have profound anti-emetic properties due 
to antagonizing histamine-1 receptors in the CNS. However, because of 
untoward sedative effects, the use of this drug class was very limited 
for postoperative antiemetic prophylaxis because it delayed emergence 
from general anesthesia. Twenty years later, the next phase of 
anti-emetic therapy emerged. The neuroleptic class of chlorpromazine 
drugs antagonized a variety of receptors in the CNS.3 Unfortunately the 
drug's neuroleptic effect elicits both sedation and hypotension which 
limited its use in PONV management.
The First Century of Anti-Emetic Therapy
After the discovery of anesthetic-induced PONV, 
clearly the distress of surgical patients were not positive experiences 
evidenced during the first 100 years ofthe practice of medicine. By 
1950, anesthesia practice changed to reduce the residual effects of 
drugs that contributed to PONV. Six years later, halothane, a 
non-flammable volatile gas developed for general inhalational anesthesia
 was introduced, replacing noxious anesthetics such as ether. Halothane 
contributed to a substantially-reduced PONV incidence after emergence 
from inhalational general anesthesia. Over the next 25 years, halothane 
was commonly administered in clinical anesthesia practice [4].
 During the 1980s in the US, the administration of these early 
inhalational anesthetic agents became less appealing and were gradually 
phased out as improved volatile agents were developed such as 
isoflurane, desflurane, or sevoflurane.
Evolution of PONV Prophylaxis
At the end of the 20th century, advancements in the 
prophylactic use of anti-emetic drug therapy had not progressed mainly 
because of the serious risks of drug side effects such as profound 
sedation. In the early 1990s, anesthetists preferred a novel anesthetic 
agent: propofol. This hypnotic drug is administered intravenously (IV) 
as an induction drug or total IV delivery for anesthetic maintenance. In
 addition, IV propofol has anti-emetic properties that help reduce the 
effects of PONV [4]. Propofol is still today's choice as a general anesthetic agent in contemporary anesthesia practice.
Novel Anti-Emetics
Fortunately, in the mid-1990s, anesthesiologists focused on the promising new class of anti-emetics, the 5-HT3-serotonin
 receptor antagonists introduced to oncologists for the treatment of 
chemotherapy-induced nausea and vomiting (CINV). These drugs block the 
5-HT3-serotonin receptors, which are highly- specific 
emetogenic receptors in the chemoreceptor trigger zone (CTZ). 
Clinically, the 5-HT3-receptor antagonists produced an anti-emetic effect with little to no side effects, with a relatively good safety profile [5].
Since the mid-1990s, the traditional anti-emetic 
therapy chosen by most anesthesiologists and certified registered nurse 
anesthetists (CRNAs) to mitigate the incidence of PONV, include the 
serotonin 5-HT3-receptor antagonists such as ondansetron 
(Zofran®), granisetron (Kytril®) or dolasetron (Anzemet®). In addition, 
anesthesiologists and CRNAs use a multi-modal strategy that includes 
dexamethasone, a steroid drug that is known to have anti-emetic 
properties to enhance the efficacy of 5-HT3 prophylactic 
therapy. Due to multiple emetic receptors that can be stimulated during 
anesthesia, the management of PONV requires multi-modal strategies using
 a combination of antiemetic drugs to help ameliorate PONV such as 5-HT3-receptor antagonists, especially in the high-risk patient population [5]. These type of anti-emetics help block the serotonin receptors throughout the gut and CNS that trigger nausea and vomiting.
Short Duration of PONV Prophylaxis Efficacy
Much evidence published over the last 15 years describes the limited efficacy and duration of action of the traditional 5-HT3-receptor
 antagonists, including dexamethasone used in a multi-modal anti-emetic 
therapy regimen. Initially anesthetists thought that 5-HT3 
antagonists should be preemptively administered, prior to the induction 
of anesthesia. However, because of the drug's relatively short duration 
of PONV efficacy, later practice evolved to administer prophylaxis just 
prior to emergence of anesthesia, at the completion of surgery during 
patient skin closure.
Comparatively, the traditionally standard use of 5-HT3-
 receptor antagonists, such as ondansetron (or in combination with 
dexamethasone), currently offer some PONV prevention as well as a higher
 safety profile compared to other prophylactic drugs. Despite the import
 of the evidence-based practice of multimodal anti-emetic drug 
prophylaxis, some surgical patients continue to experience protracted 
PONV symptoms which can also interfere with patients' recovery at home 
especially after outpatient surgery [6-8].
 Clinically, an estimated 25%-30% of surgical patients are still 
impacted by PONV after general anesthesia subsequent to receiving 
prophylactic anti-emetic medications [9].
 In addition, one-third or even up to 35%-49% of patients undergoing 
outpatient surgery experience nausea and vomiting after they are 
discharged. Largely because patients returning home from outpatient 
surgery do not have access to anti-emetic therapy [9,10].
Expanding Anti-Emetic Therapy
The relatively new phenomenon known as post-discharge
 nausea and vomiting (PDNV) has become a significant concern to 
practitioners because of the growing number of outpatient and short-stay
 surgical procedures. Anesthesiologists, CRNAs, and especially 
peri-operative nurses continue to be confronted with patients’ 
complications of PONV and PDNV, despite modifying dosages or 
combinations of anti-emetic therapy
After discharge from outpatient surgery, extended 
antiemetic benefits are not solving the PDNV problem at home.7 Clinical 
options for achieving anti-emetic efficacy in the postdischarge period 
include newer anti-emetics which are either very expensive, such as 
aprepitant (Emend®), palonesetron (Aloxi®), or transdermal scopolamine [11].
 However, the scopolamine patch may have the potential of temporarily 
imposing adverse quality of life issues (i.e., blurred vision or 
extremely dry mouth) [12].
Enhancing patient satisfaction, providing 
cost-benefits and minimizing drug side effects are paramount for a 
worthy solution to the recalcitrant PONV problem. Use of other 
clinically- developed multi-modal PONV techniques that enable patients 
to overcome the anesthetic-induced difficulties associated with surgery 
can become part of a novel and efficacious multi-modal prophylaxis 
strategy for anti-emesis [13].
Effective emetic prophylaxis management today 
requires refinement for at-risk surgical patients who require enhanced 
protection against the episodic severity of further PONV and PDNV 
suffering. Current published PONV guidelines require an upgrade of 
additional PONV techniques to mitigate the effects of both 
post-operative problems. Over the last 15 years, evidence reveals that 
prophylactic drug therapy alone is not the complete solution in 
substantially preventing the incidence of PONV and PDNV. The PONV 
guidelines offer strategic insight into identifying at-risk surgical 
patients. However, the existing prophylactic multi-modal drug treatment 
strategy model has not resulted in a complete effect of a clear and 
definitive solution to extensively improving patient recovery from 
deleterious nausea and vomiting in the post-operative period [13].
The legacy of PONV prophylaxis today is compounded by
 the growing concern of PDNV occurrences at home for surgical patients. 
The implication for expanded anti-emetic coverage is readily apparent in
 view of current clinical PONV/PDNV events. Additional multi-modal PONV 
techniques are currently available to fill the vacuum of patient need 
due to inadequate efficacy of drug therapy. Clinically-proven and FDA 
approved prescription and/or over-the-counter (OTC) main stream, 
multi-modal PONV techniques implemented as part of the multi-modal 
anesthetic plan, would serve to improve overall PONV management 
conditions
The clear implication is that intervention other than
 further pharmacotherapy is necessary to reduce nausea and vomiting 
symptoms for surgery patients. Other clinically-proven, main stream 
multi-modal PONV techniques lead these efforts. Clearly a fundamental 
serious reevaluation is necessary to achieve an enhanced quality of PONV
 outcomes management compared to drug treatment options alone [13].
PONV Pressure Point Therapy
Pressure Point, Inc. is a global medical 
device company specializing in mainstream acu-point stimulation strips, 
which improve multi-modal anesthetic techniques associated with the 
complexity common problem of post-operative nausea and vomiting. The 
company introduced its Pressure Right© acupressure 
point-stimulation product in 2011 after receiving market clearance from 
the FDA as a prescribed technique representing an essential part of the 
anesthetic plan for surgery patients. In 2014, Pressure Point 
subsequently received market clearance as an OTC technique for the 
prevention of nausea and vomiting.
As part of a multi-modal strategy for patients 
undergoing laparoscopic surgery, a high quality, randomized, 
double-blind, sham-controlled study reported that the use of Pressure 
Right© demonstrated a statistically meaningful, absolute risk reduction 
of PONV for surgical patients as long as 72 hours postoperatively [14]. The study further confirmed the direct result of prophylaxis with Pressure Right©
 revealed a multi-modal PONV effect to substantially reduce the main 
stream requirements for expensive rescue-drug therapies. As a result, a 
broader patient satisfaction with PONV prevention was reported among 
Pressure Right© study subjects.
Prior to the introduction of the multi-modal Pressure
 Right© acu-stimulation strip in 2011 for the 72-hour prevention of 
PONV, a plethora of research had been published on the efficacy of 
acu-stimulation for PONV [14-16].
 Several incipient versions of acu-stimulation offered significant 
benefits and few, if any risks. However, the early product models were 
limited in duration for multi-modal nausea prophylaxis for surgical use 
and patient suitability for PONV prevention.
Pressure Right's® adaptive adhesive technique 
uses 3M™ material that's been on the market since 1970, which is safe 
from skin irritation, blistering, or pain when applied to the skin for 
extended use.
The Pressure Right® randomized, double-blind, sham- 
controlled study effectively combined PC6 acustimulation and PONV 
antiemetic therapy versus antiemetic therapy and demonstrated improved 
PONV patient outcomes despite the use of an insensitive binary method 
(Yes or No) study response to assess postoperative nausea [14].
In a recent Cochrane review of PC6 acustimulation 
clinical data of at least 39 trials, 4622 participants, compared to sham
 treatment, it confirmed PC6 acustimulation techniques significantly 
reduced the incidence of nausea, vomiting and the need for rescue 
antiemetics postoperatively. The Cochrane author’s conclusion recommends
 more high-quality trials involving the combination of acustimulation 
and antiemetic drug therapy compared to drug prophylaxis to determine 
the combination’s clinical PONV therapy future impact [17].
Outside the US today, Pressure Point© has overseas 
distribution partners targeting the anesthetic market for prevention of 
PONV for at-risk surgical patients. Research and expanding use has 
proven Pressure Right© a high-quality competitive choice in PONV 
management.
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