4/2/2019 Strangulation Injuries - StatPearls - NCBI Bookshelf

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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-.

Strangulation Injuries
Roberta J. Dunn; William Smock.

Author Information
Last Update: October 27, 2018.

Introduction
Given that strangulation injuries may be a result of a suicide attempt, patients may necessitate
being placed on a psychiatric hold or need immediate emergency department psychiatric
evaluation. These patients also require that suicide precautions be taken if they are admitted to
the hospital. Strangulation injuries may also be a result of a criminal act. When these patients
present to the emergency department, notification of the appropriate law enforcement agencies
should also occur.

Etiology
Strangulation is defined as the compression of blood or air-filled structures which impedes
circulation or function. In this summary, strangulation will refer to compression of anatomical
neck structures leading to asphyxia and neuronal death. Strangulation injuries can be divided into
several categories. These include hanging injuries, manual strangulation, and ligature injuries.

Hanging injuries can be divided further into specific categories. Complete hanging is defined by
the full weight of the patient being suspended by the neck. Incomplete hanging injuries
encompass all injuries in which the patient is supported partially by another object such as the
ground or furniture. For centuries hanging has been used in the penal systems as a form of
punishment. The term “well-hung” referred to the erection a male experienced after a proper
hanging was performed. This method of execution usually involved dropping the person from a
height equal to or greater than their height, and this often resulted in spinal fractures, spinal
trauma, and spinal shock resulting in priapism.

Ligature and manual strangulation injuries occur when a force that is independent of the patient’s
body is applied to the neck. Strangulation injuries can also be divided into categories of intent.
These include homicidal, suicidal, accidental, and auto-erotic.

Epidemiology
Hanging injuries are the second most common cause of suicide in the United States; whereas,
gunshot wounds are the leading cause. Males are more likely to commit suicide in both of these
manners. The exact epidemiology of manual strangulation is challenging to quantify. Women in
abusive relationships are at the greatest risk of this type of injury. The incident of hanging
injuries has been increasing in the United States over the past several years. The popularity of
“choking games” amongst pre-teens and teens has also affected the escalation of these injuries.

Pathophysiology
The underlying cause of strangulation morbidity and mortality is cerebral hypoxemia and death.
However, anatomic neck structures must be fully understood to evaluate the complex
mechanisms of injuries in strangulation. Each structure has different weight capacities it can
withstand before the collapse. Cervical spine fractures most often result in complete hangings
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where the patient is dropped from a significant height. As previously stated, this height is usually
greater than or equal to the patient’s height. Fracture of the second cervical vertebrae, otherwise
known as the “hangman’s fracture,” leads to internal decapitation and immediate death. This
pathologic result of hanging injury is less common than when compared to injuries which cause
damage to other vital structures.

There are numerous anatomic neck structures that, when collapsed, can cause morbidity and
mortality in hanging injuries. Jugular veins collapse under 4.4 pounds of pressure. Carotid
arteries collapse under 5.5 to 22 pounds of pressure. The vertebral arteries will collapse under 18
to 66 pounds of pressure. The trachea will collapse under 33 pounds of pressure. The cricoid
cartilage will fracture under 45 pounds of pressure. The collapse of each of these vital structures
can lead to immediate death, as well as delayed complications. Damages to both anterior and
posterior ligaments and cervical spine dislocations have been documented as a result of
strangulation injuries. Direct spinal cord injury, hematoma, or hemorrhage can both cause
immediate death and paralysis.

Acute death will ensue when compression or occlusion of the trachea occurs. In the past, this was
proposed as the mechanism of mortality in most strangulation injuries. Swelling to the airway
and surrounding structures may also lead to acute or delayed death. Death has been documented
up to 36 hours after initial strangulation injuries. Compromise to vascular structures has been
proven to cause significant morbidity and mortality. This has been proven in tracheostomy
patients who have committed suicide. Death in these cases did not involve compression of the
trachea or airway due to the presence of an intact tracheostomy.

Compression of the jugular veins results in acute death by causing cerebral hypoxia followed by
loss of muscle tone. Once muscle tone is compromised, increased pressure is applied to both the
carotid arteries and trachea. Direct compression of the carotid arteries also leads to decrease or
loss of cerebral blood flow and brain death. Direct pressure on the carotid sinuses causes a
systemic drop in blood pressure, bradycardia, and other arrhythmias. Consequences are anoxic
and hypoxic brain injury death.

Many of the martial arts “submission holds” are known to place direct pressure to these vascular
structures primarily and can result in strangulation injuries. There can be long-term consequences
of strangulation injuries due to vascular compromise as well. Long-term anoxic brain injury,
thrombotic stroke, dissection, and aneurysm of vessels can all cause significant morbidity.

Toxicokinetics
Strangulation injuries, whether accidental or intentional may also be compounded by
toxicological pathology as well. Many times alcohol and/or prescription and non-prescription
drugs may have been ingested by the patient at or around the time of injury. Many of these
substances may also cause central nervous depression and contribute to altered mental status.
Underlying life-threatening overdoses with acetaminophen, aspirin, and tricyclic antidepressants
can cause severe metabolic disturbances and complicate strangulation injuries.

History and Physical

The history of a strangulation injury may be obtained from the patient, witnesses, family or
friends, first responder personnel, or a combination of the above. Proper history will facilitate
proper management. If possible, determine whether the strangulation was a manual, ligature, or
hanging injury. Incomplete versus complete hanging injuries should also be differentiated. If the
injury is a complete hanging, the height of drop should be assessed. Associated injuries and
ingestion need to be evaluated. Obtaining approximate time of injury is also essential. The
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patient’s initial on-scene presentation, resuscitative efforts initiated, and patient stability or
decompensation en route will also aid the practitioner to initiate proper management.

Physical examination may include one or more of the following “hard signs” of strangulation:

Head, Eyes, Ears, Nose, and Throat

Visual disturbances

Conjunctival or facial petechial hemorrhages

Swollen tongue or oropharynx

Foreign body (blood, vomit, tissue) in oropharynx

Facial edema, lacerations, abrasions, ecchymosis

Neck abrasions, edema, lacerations or ligature marks

Tenderness to palpation over larynx

Hoarseness or stridor

Subcutaneous edema or crepitus

Cardiovascular

Cyanosis or hypoxia

Arrhythmias

Respiratory distress

Crackles or wheezes

Cough

Neurologic

Altered mental status

Seizures

Stroke-like symptoms

Incontinence

Evaluation
Once the patient is stabilized, laboratory and radiologic studies can aid in determining the
severity of the injury. Laboratory studies may include complete blood count (CBC), CMP,
coagulation studies, BHcg, toxicology panel (alcohol, drug, aspirin, and Tylenol levels), lactic
acid, and ABG. CT is widely available and is the first line of radiologic evaluation of
strangulation injuries. CT Angiogram of the carotid and vertebral arteries is the gold standard in
care. This allows for evaluation of vascular and bony structures.

CT of the neck with contrast is less specific than CT Angiogram but will evaluate bony
structures and vascular structures to a degree. Non-contrast CT of the brain will evaluate for
stroke but is more sensitive for intracranial hemorrhage than for smaller ischemic strokes. Non-
contrast CT scan of the brain will identify large areas of the infarct.

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MRA of the neck is another imaging modality option, although it is less available in smaller and
rural centers, and it is also more time-consuming than CT to complete. It is also less sensitive
than CTA of the neck in evaluating vessels. MRI of the neck poses similar availability issues. It
has less sensitivity than CTA in evaluating vascular structures; however, it is the most accurate
study to evaluate soft tissues of the neck. MRI/MRA of the brain is the most sensitive modality
in evaluating both global and anoxic brain injury, ischemic stroke and, intracranial hemorrhage.

Carotid doppler is not recommended for evaluation of strangulation injuries due to its inability to
completely evaluate all of the possibly affected vascular structures. Plain chest radiography is
also recommended in patients who have required intubation or are in respiratory distress.

Treatment / Management
The primary survey, as in any traumatic injury, should begin with an evaluation of the patient’s
airway, breathing, and circulation. Immediate resuscitative interventions should take priority over
radiologic studies. If none of the “hard signs” are present, radiologic studies are not always
necessary. After evaluation in the emergency department, the patient may be discharged with
strict return precautions. If the patient presents with any of the “hard signs” of strangulation
injury, laboratory and radiologic evaluation must be performed.

If the radiologic studies are completely negative, disposition should be based on the patient’s
clinical condition. Asymptomatic patients may be discharged after Emergency Department
evaluation with strict return precautions and in-home monitoring by family or friends.
Symptomatic patients with normal radiologic studies should either be admitted to the hospital or
the emergency department observation unit, if available, for further monitoring.

Patients with abnormal radiologic studies should be admitted to the hospital to the appropriate
level of care. The patient may require telemetry, intensive care unit step-down unit, or the
intensive care unit. Specialists should also be consulted based on the injuries. This may include
trauma surgery, neurosurgery, neurology, otolaryngology, and psychiatry. Any overdoses or
metabolic disturbances warrant their specific and appropriate antidotes or symptomatic
therapeutic interventions.

Pearls and Other Issues

Given that strangulation injuries may be a result of a suicide attempt, patients may necessitate
being placed on a psychiatric hold or need immediate emergency department psychiatric
evaluation. These patients also require that suicide precautions be taken if admitted to the
hospital. Strangulation injuries may also be a result of a criminal act. When these patients present
to the emergency department, notification of the appropriate law enforcement agencies should
also occur in the emergency department.

Questions
To access free multiple choice questions on this topic, click here.

References
1. Eş H, Şahin MF, Özdemir E. Laryngohyoid Fractures in Fatal Nonhomicidal Falls From a
Height. Am J Forensic Med Pathol. 2017 Dec;38(4):289-293. [PubMed: 28926347]
2. Hlavaty L, Sung L. Strangulation and Its Role in Multiple Causes of Death. Am J Forensic
Med Pathol. 2017 Dec;38(4):283-288. [PubMed: 28857762]
3. Kim TH, Lee SH, Kim DH, Kim SC, Jin W, Kim SY, Shin SH, Lee SB. Non-aneurysmal and
non-traumatic subarachnoid hemorrhage after attempted suicide by incomplete hanging. Clin
https://www.ncbi.nlm.nih.gov/books/NBK459192/ 4/8
4/2/2019 Strangulation Injuries - StatPearls - NCBI Bookshelf

Exp Emerg Med. 2017 Mar;4(1):56-59. [PMC free article: PMC5385506] [PubMed:
28435903]
4. Wu XM, Zhang XD, Yun LB, Liu M, Yi XF. Sudden Death From Ruptured Intracranial
Vascular Malformations During Mechanical Asphyxia: A Domestic Violence Case Report.
Am J Forensic Med Pathol. 2017 Mar;38(1):35-38. [PubMed: 28005586]
5. Skinner R, McFaull S, Draca J, Frechette M, Kaur J, Pearson C, Thompson W. Suicide and
self-inflicted injury hospitalizations in Canada (1979 to 2014/15). Health Promot Chronic
Dis Prev Can. 2016 Nov;36(11):243-251. [PMC free article: PMC5432047] [PubMed:
27882859]
6. Castiglioni C, Baumann P, Fracasso T. Acute pulmonary emphysema in death by hanging: a
morphometric digital study. Int. J. Legal Med. 2016 Sep;130(5):1281-5. [PubMed:
27448112]
7. Flieger A, Kölzer SC, Plenzig S, Heinbuch S, Kettner M, Ramsthaler F, Verhoff MA. Bony
injuries in homicide cases (1994-2014). A retrospective study. Int. J. Legal Med. 2016
Sep;130(5):1401-8. [PubMed: 27401087]
8. Zilkens RR, Phillips MA, Kelly MC, Mukhtar SA, Semmens JB, Smith DA. Non-fatal
strangulation in sexual assault: A study of clinical and assault characteristics highlighting the
role of intimate partner violence. J Forensic Leg Med. 2016 Oct;43:1-7. [PubMed:
27376175]
9. Armstrong M, Strack GB. Recognition and Documentation of Strangulation Crimes: A
Review. JAMA Otolaryngol Head Neck Surg. 2016 Sep 01;142(9):891-7. [PubMed:
27308820]
10. Ma J, Jing H, Zeng Y, Tao L, Yang Y, Ma K, Chen L. Retrospective analysis of 319 hanging
and strangulation cases between 2001 and 2014 in Shanghai. J Forensic Leg Med. 2016
Aug;42:19-24. [PubMed: 27219113]
11. Mcquown C, Frey J, Steer S, Fletcher GE, Kinkopf B, Fakler M, Prulhiere V. Prevalence of
strangulation in survivors of sexual assault and domestic violence. Am J Emerg Med. 2016
Jul;34(7):1281-5. [PubMed: 27162112]
12. Shetty U, Deepak M, Hussain SA, Usmani H, Osama M, Pereira KG, Menezes RG.
Survival following accidental scarf strangulation. Med Leg J. 2016 Sep;84(3):150-2.
[PubMed: 27048761]
13. Unal EO, Koc S, Unal V, Akcan R, Javan GT. Violence against women: A series of autopsy
studies from Istanbul, Turkey. J Forensic Leg Med. 2016 May;40:42-6. [PubMed:
27016881]
14. Kanchan T, Raghavendra Babu YP, Atreya A, Acharya J. Ligature mark on the face -
forensic implications. Med Leg J. 2016 Sep;84(3):138-41. [PubMed: 26968980]
15. Meel Banwari L. A case report on near manual strangulation and glasgow coma scale. Afr
Health Sci. 2015 Sep;15(3):1038-40. [PMC free article: PMC4765444] [PubMed:
26957999]
16. Fais P, Giraudo C, Viero A, Miotto D, Bortolotti F, Tagliaro F, Montisci M, Cecchetto G.
Micro computed tomography features of laryngeal fractures in a case of fatal manual
strangulation. Leg Med (Tokyo). 2016 Jan;18:85-9. [PubMed: 26832384]
17. Pritchard AJ, Reckdenwald A, Nordham C. Nonfatal Strangulation as Part of Domestic
Violence: A Review of Research. Trauma Violence Abuse. 2017 Oct;18(4):407-424.
[PubMed: 26721886]
18. Sashko SY, Krut' MI, Zaraf'yants GN, Lebedeva TV. [Forensic medical diagnostics of the
impact of the ligatures made from different materials in the cases of strangulation
asphyxia]. Sud. Med. Ekspert. 2015 Sep-Oct;58(5):9-11. [PubMed: 26710507]
19. Suffla S, Seedat M. The epidemiology of homicidal strangulation in the City of
Johannesburg, South Africa. J Forensic Leg Med. 2016 Jan;37:97-107. [PubMed:
https://www.ncbi.nlm.nih.gov/books/NBK459192/ 5/8
4/2/2019 Strangulation Injuries - StatPearls - NCBI Bookshelf

26654837]
20. Madea B, Schmidt P, Kernbach-Wighton G, Doberentz E. Strangulation--Suicide at the
wheel. Leg Med (Tokyo). 2015 Nov;17(6):512-6. [PubMed: 26594000]
21. Wöllner K, Ortmann J, Kernbach-Wighton G, Madea B. [Suicidal fall from height after
restraint or accident?]. Arch Kriminol. 2015 Sep-Oct;236(3-4):130-5. [PubMed: 26548037]
22. Pramanik P. An Unusual Method of Suicidal Ligature Strangulation. J. Forensic Sci. 2016
Jan;61(1):274-6. [PubMed: 26211537]
23. Pollak S, Thierauf-Emberger A. Homicidal assault to the neck with subsequent simulation
of self-hanging. Forensic Sci. Int. 2015 Aug;253:e28-32. [PubMed: 26159256]
24. Das S, Patra AP, Shaha KK, Sukumar S, Chaudhari VA, Rahman NA. Occupational death
due to bilateral carotid artery occlusion - a medico-legal case report. J Forensic Leg Med.
2015 May;32:30-3. [PubMed: 25882146]
25. [Injuries and vital reactions patterns in hanging]. Srp Arh Celok Lek. 2015 Jan-Feb;143(1-
2):93-9. [PubMed: 25845260]
26. Naimo P, O'Donnell C, Bassed R, Briggs C. The use of computed tomography in
determining development, anomalies, and trauma of the hyoid bone. Forensic Sci Med
Pathol. 2015 Jun;11(2):177-85. [PubMed: 25711290]
27. YadollahiKhales G, Ghorbani A, Borhani-Haghighi A. Tinnitus 3 years after strangulation.
J. Nerv. Ment. Dis. 2015 Feb;203(2):154-5. [PubMed: 25629667]
28. AlBuhairan F, AlMutairi A, Al Eissa M, Naeem M, Almuneef M. Non-suicidal self-
strangulation among adolescents in Saudi Arabia: Case series of the choking game. J
Forensic Leg Med. 2015 Feb;30:43-5. [PubMed: 25623195]
29. Re L, Birkhoff JM, Sozzi M, Andrello L, Osculati AM. The choking game: A deadly game.
Analysis of two cases of "self-strangulation" in young boys and review of the literature. J
Forensic Leg Med. 2015 Feb;30:29-33. [PubMed: 25623192]
30. Sharma A. Rickshaw scarf strangulation. Med Leg J. 2015 Jun;83(2):109-10. [PubMed:
25568171]
31. Foley A. Strangulation: know the symptoms, save a life. J Emerg Nurs. 2015 Jan;41(1):89-
90. [PubMed: 25555700]
32. Kumral B, Ozdes T, Avsar A, Buyuk Y. Accidental deaths by hanging among children in
Istanbul, Turkey: retrospective analysis of medicolegal autopsies in 33 years. Am J Forensic
Med Pathol. 2014 Dec;35(4):271-4. [PubMed: 25310372]
33. Driessen A, Probst C, Sakka SG, Eikermann C, Mutschler M. [Bilateral carotid artery
dissection in a kite surfer by strangulation with the kite lines]. Unfallchirurg. 2015
Jun;118(6):567-70. [PubMed: 25135706]
34. Tzimas I, Bajanowski T, Pollak S, Trübner K, Thierauf A. Suicidal ligature strangulation
using gymnastics bands. Int. J. Legal Med. 2014 Mar;128(2):313-6. [PubMed: 24429766]
35. Radosavkić R, Vapa D, Pilija V. [Homicide or suicide by strangulation--case report]. Med.
Pregl. 2013 Sep-Oct;66(9-10):392-5. [PubMed: 24245448]
36. Faugno D, Waszak D, Strack GB, Brooks MA, Gwinn CG. Strangulation forensic
examination: best practice for health care providers. Adv Emerg Nurs J. 2013 Oct-
Dec;35(4):314-27. [PubMed: 24176831]
37. Zorro AR. Suicidal strangulation by double ligature: a case report. Med Sci Law. 2014
Apr;54(2):110-2. [PubMed: 24052004]
38. Aspalter M, Linni K, Domenig CM, Mader N, Klupp N, Hölzenbein TJ. Successful repair
of bilateral common carotid artery dissections from hanging. Ann Vasc Surg. 2013
Nov;27(8):1186.e7-15. [PubMed: 23972634]
39. Le Blanc-Louvry I, Papin F, Vaz E, Proust B. Cervical arterial injury after strangulation--
different types of arterial lesions. J. Forensic Sci. 2013 Nov;58(6):1640-3. [PubMed:
23865759]
https://www.ncbi.nlm.nih.gov/books/NBK459192/ 6/8
4/2/2019 Strangulation Injuries - StatPearls - NCBI Bookshelf

40. Cobzeanu MD, Palade D, Manea C. Epidemiological features and management of complex neck
trauma from an ENT surgeon's perspective. Chirurgia (Bucur). 2013 May-Jun;108(3):360-4.
[PubMed: 23790785]
41. Lebreton-Chakour C, Godio-Raboutet Y, Torrents R, Chaumoitre K, Boval C, Bartoli C,
Adalian P, Piercecchi-Marti MD, Thollon L. Manual strangulation: experimental approach
to the genesis of hyoid bone fractures. Forensic Sci. Int. 2013 May 10;228(1-3):47-51.
[PubMed: 23597739]
42. Turkmen N, Eren B, Uyaniker ZD, Ergonen AT. An uncommon suicide method: self-
strangulation. Med Arch. 2012;66(6):423-4. [PubMed: 23409528]
43. Pramod Kumar GN, Arun M, Manjunatha B, Balaraj BM, Verghese AJ. Suicidal
strangulation by plastic lock tie. J Forensic Leg Med. 2013 Jan;20(1):60-2. [PubMed:
23217378]
44. McLean M. Have you missed signs in a victim of strangulation? Alta RN. 2012
Fall;68(3):18-9. [PubMed: 23162988]
45. Joshi M, Thomas KA, Sorenson SB. "I didn't know I could turn colors": Health problems
and health care experiences of women strangled by an intimate partner. Soc Work Health
Care. 2012;51(9):798-814. [PubMed: 23078012]
46. Briddell J, Mallon A, DeFatta RA, Chowdhury F, Nagorsky M. Dysphagia after
strangulation. Ear Nose Throat J. 2012 Sep;91(9):E30-1. [PubMed: 22996717]
47. Taslimi R, Daneshbod Y, Mirfazaelian H. Facial petechia as a sign of strangulation in
trauma victims. Emerg Med J. 2013 Apr;30(4):311. [PubMed: 22983981]
48. Badiadka KK, Kanchan T, D'Souza DH, Subhash K, Vasu S. An unusual case of self-
strangulation by ligature. J Forensic Leg Med. 2012 Oct;19(7):434-6. [PubMed: 22920771]
49. Ramchand T, Choudhry OJ, Shukla PA, Tomovic S, Kuperan AB, Eloy JA. Management of
hyoid bone fractures: a systematic review. Otolaryngol Head Neck Surg. 2012
Aug;147(2):204-8. [PubMed: 22691692]
50. Godin A, Kremer C, Sauvageau A. Fracture of the cricoid as a potential pointer to
homicide. A 6-year retrospective study of neck structures fractures in hanging victims. Am
J Forensic Med Pathol. 2012 Mar;33(1):4-7. [PubMed: 22442828]
51. Bergin A, Berkowitz R. Domestic violence in military families: non-fatal strangulation. Md
Med. 2012;13(3):19, 29. [PubMed: 23477262]
52. Nor FM, Das S. Planned complex suicide: self-strangulation and fall from height. J Forensic
Leg Med. 2011 Oct;18(7):336-9. [PubMed: 21907941]
53. Sorokin V, Persechino F, DeRoux SJ, Greenberg MJ. Suicidal ligature strangulation
utilizing cable ties: a report of three cases. Forensic Sci Med Pathol. 2012 Mar;8(1):52-5.
[PubMed: 21901550]
54. Lemyze M, Palud A, Favory R, Mathieu D. Unintentional strangulation by a cervical collar
after attempted suicide by hanging. Emerg Med J. 2011 Jun;28(6):532. [PubMed:
21183526]
55. Shields LB, Corey TS, Weakley-Jones B, Stewart D. Living victims of strangulation: a 10-
year review of cases in a metropolitan community. Am J Forensic Med Pathol. 2010
Dec;31(4):320-5. [PubMed: 21171201]
56. Jänisch S, Heine J, Günther D, Germerott T. [Examination reports on survived strangulation
cases]. Arch Kriminol. 2010 Sep-Oct;226(3-4):73-82. [PubMed: 21121118]
57. Molacek J, Baxa J, Houdek K, Ferda J, Treska V. Bilateral post-traumatic carotid dissection
as a result of a strangulation injury. Ann Vasc Surg. 2010 Nov;24(8):1133.e9-11. [PubMed:
20800431]
58. Sarma K, Kola S. The socio-demographic profile of hanging suicides in Ireland from 1980
to 2005. J Forensic Leg Med. 2010 Oct;17(7):374-7. [PubMed: 20851356]
59. Molacek J, Baxa J, Houdek K, Ferda J, Treska V. Bilateral post-traumatic carotid dissection
https://www.ncbi.nlm.nih.gov/books/NBK459192/ 7/8
4/2/2019 Strangulation Injuries - StatPearls - NCBI Bookshelf

as a result of a strangulation injury. Ann Vasc Surg. 2010 Nov;24(8):1133.e9-11. [PubMed:

20800431]

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