Acupuncture and Sepsis

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


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In electroacupuncture, an electrical stimulator connects by a wire to an electrode attached to the needle shaft.

Photos courtesy of Dr. Narda Robinson

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.

FOOTNOTES

[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.

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