What You Need to Know Acupuncture and Sepsis

By Narda Robinson, DO, DVM

Unless sepsis is on your radar, you might well miss it.

Sepsis is defined as “a syndrome of microbial infection complicated by systematic inflammation which may subsequently lead to organ dysfunction, shock, and death.”¹ The cat with a severe bite wound, the dog with peritonitis and the puppy with parvo may all develop sepsis, but their clinical presentations may vary dramatically.

In addition to interspecies differences, diagnosis can prove difficult because of the many ways in which sepsis mimics critical conditions. The diagnosis also eludes clinicians who fail to see the big picture of constellating clinical, physiologic and laboratory changes signaling sepsis. This accounts for many missed opportunities for early intervention and life-saving care.²

That said, even after sepsis is diagnosed, treatment can be daunting and ineffectual. In humans, sepsis leads to over 750,000 hospital admissions and 200,000 deaths each year.  The comparative incidence of sepsis in dogs and cats is unknown.^3,4

How it Happens

How sepsis happens is not fully understood but likely involves an over-exuberant release of inflammatory cytokines in response to a provocation, whether infection, ischemia, injury, trauma or cancer.⁵ The patient may develop SIRS, i.e., systemic inflammatory response syndrome and progress to MODS, or multiple organ dysfunction syndrome, another condition with high risk of significant morbidity and mortality.⁶

Should the patient survive, s/he may enter a state of sepsis, septic shock (characterized by refractory arterial hypotension) or severe sepsis (associated with MODS).  All of these conditions arise, at least in part, from an overabundance of pro-inflammatory cytokines.⁷

In an effort to restore order within an immune system run amok, treatments have tended to focus more on managing cytokine mayhem. However, what has been missing is attention on a key feature that appears to precipitate sepsis – an imbalance in the autonomic nervous system.  

Missing the mark in this way may result in some of the unsatisfactory outcomes seen with sepsis, a condition that accounts for nearly 10 percent of overall human deaths in the U.S.⁸

Over the past decade, studies investigating novel strategies to fight inflammation have turned to supporting the parasympathetic limb of the autonomic nervous system, an ally in the battle against pro-inflammatory cytokines.  

In particular, investigators found that acetylcholine, the main neurotransmitter of the parasympathetic nervous system, inhibits the liberation of these pro-inflammatory mediators from macrophages.⁹

By analyzing the effects of selective cholinergic agonists and antagonists, scientists have shown that activation of nicotinic receptors (with nicotine) specifically suppresses inflammation much more than their muscarinic counterparts. Curiously, humans with ulcerative colitis experience a reduction in symptoms when they smoke cigarettes;¹⁰ nicotine has demonstrable anti-inflammatory effects on cells and tissues, from the nasal epithelium¹¹ to the digestive tract,¹² arthritic joints¹³ and more.   

Smoking

Of course, the dangers of smoking as well as excessive nicotine¹⁴ preclude recommending this drug clinically, especially for critically ill patients. Thus, safer means of nudging the nervous system in a pro-parasympathetic direction are needed. 

Enter electroacupuncture (EA). EA differs from dry needling (i.e., the insertion of an acupuncture needle) by having an electrical stimulator connected by a wire to an electrode attached to the needle shaft. 

The frequency and amplitude of the electrical current delivered through the needle depends on the practitioner’s neuromodulatory goals and patient tolerance, respectively. 

EA amplifies the effects of acupuncture on the peripheral, central and autonomic nervous systems. An advantage of EA is that it delivers a consistent and quantifiable input, making it ideal for the research setting. Medical acupuncturists also use EA in order to activate selective neuroanatomic pathways that engender well-documented clinical neurophysiologic shifts. 

A 2014 study reported in Nature Medicine utilized EA applied to the sciatic nerve and studied the effects of acupuncture neuromodulation on experimentally induced sepsis in a mouse model.¹⁵  In so doing, they found that somatic afferent (10Hz) electrical stimulation of the fibular nerve at the acupuncture point Zusanli (ST 36) in the cranial tibialis controlled systemic inflammation. 

It did so at least in part through vagal activation and subsequent stimulation of dopaminergic type-1 receptors. These effects contributed to the restoration of immunologic homeostasis. They outlined yet another circuit that adds to other neural-immune reflexes involving many neurologic centers, including the nucleus tractus solitarius, the hypothalamic pituitary adrenal axis, adrenergic nerves supplying lumbar spinal cord vasculature, and adrenergic nerves from the celiac ganglion that supply the spleen.¹⁶

This paper added to the growing evidential basis¹⁷ indicating the relevance of modulating the autonomic nervous system in order to assist the body in endogenously suppressing inflammatory responses.

It also emphasizes the importance of considering integrative therapies such as acupuncture and massage^18,19 for critically ill patients battling inflammation, immune dysfunction, voiding complications,²⁰ digestive disorders,²¹ pain,^{,22, 23, 24} anxiety,^{25, 26} and other issues typically experienced by this population. 

Of course, treating these highly compromised individuals requires abundant caution and care.  Clean technique is a must,²⁷ and practitioners should avoid methods of stimulation that further burden an already unstable immunologic and cardiovascular system.²⁸

That said, the risks of instituting acupuncture and massage seem infinitesimal compared to the risk of doing nothing in cases of sepsis and SIRS. 

As one author noted regarding canine sepsis:  “Owners do not want their beloved sick dog to be in pain.”²⁹

Clients should at least be provided with the option to choose supportive, integrative therapies for their hospitalized dog, cat, or other animal companion. There is little reason not to.

References

1. Nguyen SQ, Mwakalindile E, Booth JS, et al.  Automated electronic medical record sepsis detection in the emergency department.  PeerJ.  2014; DOI: 10.7717/peerj.343.
2. Nguyen SQ, Mwakalindile E, Booth JS, et al.  Automated electronic medical record sepsis detection in the emergency department.  PeerJ.  2014; DOI: 10.7717/peerj.343.
3. Otto CM and Costello M.  A fresh look at identifying sepsis in cats.  DVM 360.  September 1, 2010.  Accessed at http://veterinarymedicine.dvm360.com/vetmed/ArticleStandard/Article/detail/685811 on 06-18-14.
4. Hoskins JD.  Treatment of canine sepsis:  first identify, eradicate the cause.  DVM 360.  February 1, 2008.  Accessed at http://veterinarynews.dvm360.com/dvm/Medicine/Treatment-of-canine-sepsis-First-identify-eradicat/ArticleStandard/Article/detail/488855?contextCategoryId=171  on 06-18-14.
5. Ulloa L and Wang P.  The neuronal strategy for inflammation.  Novartis Foundation Symposium.  2007;280:223-233.
6. Osterbur K, Mann FA, Kuroki K, et al.  Multiple organ dysfunction syndrome in humans and animals.  J Vet Intern Med.  2014; doi:  10.1111/jvim.12364.
7. Ulloa L and Wang P.  The neuronal strategy for inflammation.  Novartis Foundation Symposium.  2007;280:223-233.
8. Torres-Rosas R, Yehia G, Pena G, et al.  Dopamine mediates vagal modulation of the immune system by electroacupuncture.  Nature Medicine.  2014;20(3):291-295.
9. Ulloa L and Wang P.  The neuronal strategy for inflammation.  Novartis Foundation Symposium.  2007;280:223-233.
10. Ulloa L and Wang P.  The neuronal strategy for inflammation.  Novartis Foundation Symposium.  2007;280:223-233.
11. Comer DM, Elborn JS, and Ennis M.  Inflammatory and cytotoxic effects of acrolein, nicotine, acetylaldehyde and cigarette smoke extract on human nasal epithelial cells.  BMC Pulm Med.  2014;14:32.  Doi:  10.1186/1471-2466-14-32.
12. Nemethova A, Michel K, Gomez-Pinilla PJ, et al.  Nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the beta2 nicotinic acetylcholine receptor.  PLoS One.  2013; 8(11):e79264.
13. Wu S, Luo H, Xiao X, et al.  Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine. Eur J Pharmacol.  2014;735:97-104.
14. Lin C, Yon J-M, Hong JT, et al.  4-O-methylhonokiol inhibits serious embryo anomalies caused by nicotine via modulations of oxidative stress, apoptosis, and inflammation.  Birth Defects Research (Part B).  2014;101:125-134.
15. Torres-Rosas R, Yehia G, Pena G, et al.  Dopamine mediates vagal modulation of the immune system by electroacupuncture.  Nature Medicine.  2014;20(3):291-295.
16. Chavan SS and Tracey KJ.  Regulating innate immunity with dopamine and electroacupuncture.  Nature Medicine.  2014;20(3):239-240.
17. Czura CJ and Tracey KJ.  Autonomic neural regulation of immunity. Journal of Internal Medicine.  2005;257;156-166.
18. Waters-Banker C, Butterfield TA, and Dupont-Versteegden EE.  Immunomodulatory effects of massage on nonperturbed skeletal muscle in rats.  J Appl Physiol.  2014;116:164-175.
19. Crane JD, Ogborn DI, Cupido C, et al.  Massage therapy attenuates inflammatory signaling after exercise-induced muscle damage.  Sci Transl Med.  2012;4(119):119ra13.
20. Yi WM, Chen Qi, Liu CH, et al.  Acupuncture for preventing complications after radical hysterectomy:  a randomized controlled clinical trial.  Evid Based Complement Alternat Med.  2014;2014:802134.  Doi:  10.1155/2014/802134.
21. Pfab F, Winhard M, Nowak-Machen M, et al.  Acupuncture in critically ill patients improves delayed gastric emptying:  a randomized controlled trial.  Anesth Analg.  2011;112(1):150-155.
22. Cho Y-H, Kim C-K, Heo K-H, et al.  Acupuncture for acute postoperative pain after back surgery:  a systematic review and meta-analysis of randomized controlled trials.  Pain Practice.  2014; Apr 28.  Doi: 10.1111/papr. 12208 [Epub ahead of print].
23. Kumar S, Beaton K, and Hughes T.  The effectiveness of massage therapy for the treatment of nonspecific low back pain:  a systematic review of systematic reviews.  Int J Gen Med.  2013;6:733-741.
24. Paley CA, Bennett MI, and Johnson MI.  Acupuncture for cancer-induced bone pain?  Evid Based Complement Alternat Med. 2011;2011:671043.  Doi 10.1093/ecam/neq020.
25. Nayak S, Wenstone R, Jones A, et al.  Surface electrostimulation of acupuncture points for sedation of critically ill patients in the intensive care unit – a pilot study.  Acupunct Med.  2008;26(1):1-7.
26. Zheng X, Meng JB, and Fang Q.  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(2):78-84.
27. Tseng YC, Yang YS, Wu YC, et al.  Infectious sacroilitis caused by Staphylococcus aureus following acupuncture:  a case report.  Acupunct Med.  2014; 32(1):77-80.  Doi: 10.1136/acupmed-2013-010457.
28. Jung JW, Jeon EJ, Kim JW, et al.  A fatal case of intravascular coagulation after bee sting acupuncture.  Allergy Asthma Immunol Res.  2012;4(2):107-109.
29. Hoskins JD.  Treatment of canine sepsis:  first identify, eradicate the cause.  DVM 360.  February 1, 2008.  Accessed at http://veterinarynews.dvm360.com/dvm/Medicine/Treatment-of-canine-sepsis-First-identify-eradicat/ArticleStandard/Article/detail/488855?contextCategoryId=171  on 06-18-14.