Cannabis is one of the most popular psychoactive substances in the world, consumed by an estimated 183 million people, or 3.8% of the world's population.1 In the United States, cannabis continues to stand as the most utilized recreational substance behind tobacco and alcohol, consumed by >15% of the population per year, in spite of the contentious surrounding legal atmosphere.2 Since the turn of the century, the utilization and legal status of cannabis in the United States for medical and recreational purposes has undergone substantial reform, even in the face of a federal ban that has remained in place since the Controlled Substances Act of 1970.3 The State of California's statewide legalization in 1996, in defiance of federal statute, sparked a subsequent wave of decriminalization and legalization efforts across the nation for the next two decades, and by the end of the 2010s, virtually all states had at least legalized cannabis for medically indicated use. With increasing legality and governmental tolerance came a decrease in the social stigmata surrounding cannabis’ use, causing patients to more comfortably and readily report their use to their physicians, including surgeons before elective procedures.
Chronic cannabis use has been associated with various complications that may be of interest to spine surgeons. Despite the United States’ having the highest rates of spine surgery in the world, no study has examined the effects of cannabis on patients undergoing these procedures.4 The purported association of the substance with increased airway reactivity and other markers of hampered pulmonary function, as shown in several studies, may contribute to perioperative respiratory complications, and may be especially comorbid with surgical manipulation in the mid-cervical spine.5–8 Another suggested association in the literature between cannabis use and myocardial infarction (MI) and stroke may further contribute to surgical patient morbidity,9 and the vasoconstrictive effects on the peripheral vasculature suggested by some might potentially affect wound healing and bleeding risk, particularly with the extensive venous plexus involved in the paravertebral space.6,10 The purpose of this study is to further evaluate the association between cannabis use and perioperative complications following elective spine surgeries.
The National Inpatient Sample (NIS), maintained by the United States Department of Health and Human Services Agency of Healthcare Research and Quality, is the largest all-payer inpatient database in the country. It contains data from 20% of all inpatient hospital discharges in the United States, and has been validated as being nationally representative.11–13 NIS core files contain clinical and nonclinical data elements for each hospital discharge, including coded diagnoses, comorbidities, and procedures present during the hospitalization course, length of stay, and total charges. Nonclinical demographic variables include patient race/ethnicity, age, median household income quartile of the patient's zip code, rural/urban location of hospital, and expected primary payment source (e.g., insurance type). NIS core files from years 2012 to 2015 were merged. Because the NIS is a de-identified database, this study was deemed exempt from approval by the institutional review board (IRB) at the authors’ institution.
Patient Selection and Classification
Patient records were included in the study if the list of documented inpatient procedures included common elective spine procedures, defined using International Classification of Diseases, 9th Revision (ICD-9) codes 03.09 (corresponding to decompression of the spinal canal/laminectomy), 81.0 (spinal fusion at any level), and 81.3 (re-fusion of the spine).
Patient discharge records were then aggregated based on coded diagnosis suggestive of cannabis use disorder. Those patients having a diagnosis of cannabis dependence (defined by ICD-9 code 304.3) or cannabis abuse (ICD-9 codes 305.20, 305.21, and 305.22) were grouped into cannabis use and control groups.
An Elixhauser Comorbidity Index (ECI) score, a validated marker of overall in-hospital morbidity and predictor of mortality, was calculated for each patient based on code from Thompson et al (2015).14 Specifically, the ECI factors in documented pre-operative diagnoses of HIV/AIDS, alcohol abuse, anemia, rheumatoid arthritis, cardiac arrhythmia, congestive heart failure, chronic pulmonary disease, coagulopathy, depression, diabetes, drug abuse, hypertension, hypothyroidism, liver disease, lymphoma, fluid and electrolyte disturbances, metastatic cancer, neurological disorders, obesity, paralysis, peripheral vascular disease, psychosis, pulmonary circulatory disorders, renal failure, solid tumors (without metastasis), peptic ulcer disease, valvular disease, and unintentional weight loss. Comorbid tobacco smoking status was also measured, defined using ICD-9 diagnosis codes 305.1 (tobacco use disorder) and V15.82 (personal history of tobacco use). Other baseline information collected for each patient included race, sex, age, and insurance coverage.
The endpoints of this study included documented all-cause in-hospital mortality, length of stay (in days), hospital charges (in US dollars), and discharge disposition according to uniform coding by the Healthcare Cost and Utilization Project (HCUP), which classifies disposition as home/routine, transfer to short-term hospital, discharge to a skilled nursing/intermediate care/rehabilitation center, home health care, patient leave against medical advice, or deceased. Also collected were the incidence of peri- and postoperative complications during the hospitalization course, defined by ICD-9 diagnosis code, including acute kidney injury (584∗), respiratory complications (518.5∗, a code corresponding to any pulmonary insufficiency following trauma or, in this case, surgery), thromboembolism (415.1∗), sepsis/septicemia (038.∗), MI (410∗), and neurologic complications (997.0∗, which includes postoperative anoxic brain injury and postoperative stroke).
Baseline patient characteristics were compared among the two groups using χ2 tests for categorical variables and two-tailed t tests for continuous variables. Wilcoxon rank sum tests were used in places of the latter for variables that were not normally distributed.
To control for baseline differences in patient demographics and predisposition, k-nearest neighbors propensity score matching was implemented with respect to age, race, sex, insurance type, tobacco smoker status, and Elixhauser comorbidity index, using R package MatchIt version 3.0.2. Propensity score calculation was based on a logistic regression model. This resulted in two equally sized groups. The cannabis group was compared to non-cannabis users with respect to cost and postoperative outcomes (mortality, discharge disposition, complications, and length of stay).
Throughout this study, a P value of <0.05 was utilized to determine statistical significance. Initial filtering of NIS data using ICD-9 procedure codes for spinal fusion and decompression operations was performed using SPSS Statistics, version 23 (IBM Corporation, NY), and statistical analysis was performed using R version 3.5.2 (R Foundation, Vienna, Austria).
A total of 423,978 eligible elective spine surgery patients were identified based on ICD-9 procedure codes between 2012 and 2015. Patients were stratified into cannabis users (n = 2393) non-cannabis users (n = 421,571) (Figure 1). The baseline characteristics of these unmatched cohorts are presented in Table 1. Patients with cannabis use disorder demonstrated statistically significant differences in age, sex, race, insurance coverage, ECI, and tobacco use status. Cannabis users were younger (45.3 vs. 57.4 years, P < 0.001), and were more frequently male (71.2% vs. 48.2%, P < 0.001), black/African-American or Hispanic/Latino (black/African-American: 24.1% vs. 8.8%; Hispanic/Latino: 7.4% vs. 6.2%; P < 0.001), and Medicaid or self-pay (Medicaid: 28.5% vs. 7.8%; self-pay: 8.2% vs. 1.4%; P < 0.001). Nearly three-fourths of patients in the cannabis group also were concomitant tobacco users (71.2% vs. 30.8% in the non-cannabis group, P < 0.001). However, cannabis users had lower levels of overall comorbidity, as demonstrated by lower ECI (−6.8 vs. 0.7, P < 0.001).
TABLE 1 -
Baseline Characteristics of Patients
||Cannabis Use (N = 2393)
||No Cannabis Use (N = 421,571)
|Age, y, mean (SD)
|Sex, female, no. (%)
|Race, no. (%)
| Asian/Pacific Islander
| Native American
|Insurance coverage, no. (%)
| Private insurance
| No charge
|Concomitant tobacco smoker, no. (%)
|Elixhauser Comorbidity Index, mean (SD)
SD indicates standard deviation.
Given the significant differences in the baseline characteristics of the primary cohorts, propensity score matching was performed to allow for greater comparison between groups (Figure 2). Propensity score matching generated equal cohorts of 2184 patients which were balanced in regard to demographics and comorbidities (Table 2). Cannabis use disorder was not associated with a statistically significant impact on inpatient mortality (0.3% vs. 0.09%, P = 0.095). However, cannabis use was associated with a statistically significant impact on discharge disposition (P < 0.001), demonstrating increased odds of discharge to skilled nursing facilities or rehabilitation facilities (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.1–1.5). However, it was associated with decreased odds of discharge to home health care (OR 0.7, 95% CI 0.6–0.9).
TABLE 2 -
Peri- and Postoperative Outcomes and Complications
||Cannabis Use (N = 2184)
||No Cannabis Use (N = 2184)
||OR (95% CI)
|In-hospital mortality, all-cause, N (%)
|Discharge disposition, N (%)
| Transfer to short-term hospital
| Skilled nursing/rehabilitation facility
| Home health care
| Against medical advice
|Length of stay, days, mean (SD)
|Hospital charges, USD, mean (SD)
|Complications, N (%)
| Acute kidney injury
| Respiratory complications
| Thromboembolic events
| Myocardial infarction
| Neurologic complications
CI indicates confidence interval; OR, odds ratio; SD, standard deviation.
The cannabis use cohort also demonstrated increased length of stay (7.1 vs. 5.2 days, P < 0.001) and greater hospital charges ($137,631.30 vs. $116,112.60, P < 0.001). Finally, an analysis of inpatient complications revealed that cannabis use disorder was associated with increased rates of respiratory complications (4.7% vs. 2.3%, P < 0.001), thromboembolic events (1.9% vs. 0.9%, P = 0.005), sepsis (2.7 vs. 1.7%, P = 0.031), and neurologic complications (i.e., postoperative stroke and/or anoxic brain injury, 1.1% vs. 0.3%, P = 0.007), but not acute kidney injury or MI. Cannabis users had an approximately two-fold increase in odds of respiratory complications (OR 2.0, 95% CI 1.4–2.9) and thromboembolism (OR 2.2, 95% CI 1.2–4.0), a nearly three-fold increase in odds of postoperative neurologic events (OR 2.9, 95% CI 1.2–7.5).
In our large retrospective cohort analysis of peri- and postoperative outcomes among patients with active cannabis use disorder undergoing elective spine surgery, we found there to be significantly worse postoperative respiratory complications, septicemia/sepsis, thromboembolism, neurologic complications such as stroke and anoxic brain injury, as well as discharge disposition when compared to patients without cannabis use, despite no significant difference in inpatient mortality after controlling for comorbid tobacco use. Additionally, patients with cannabis use disorder were more likely to be discharged to a skilled nursing facility (SNF) or rehabilitation facility and less likely to be discharged to home health care. Patients with cannabis use disorder also had significantly longer lengths of stays in the hospital as well as higher overall hospital charges. Given that analyses were done on propensity-matched cohorts that were balanced with regard to both patient demographics and their baseline comorbidities, these findings are particularly alarming and may warrant careful preoperative, intraoperative, and postoperative surveillance for patients with cannabis use disorder undergoing elective spine surgeries. Specific management for patients with known active cannabis use disorder may help reduce morbidity and mortality for these patients while also alleviating healthcare burden by shortening length of stay and decreasing hospital charges.
Prevalence, Psychosocial Factors, and the Doctor–Patient Relationship
The prevalence of cannabis use and cannabis use disorder have drastically increased over the course of the past two decades. Hasin et al (2015) found that the rates of both cannabis use and diagnosed cannabis use disorder nearly doubled between 2001 to 2002 and 2012 to 2013 from 4.1% to 9.5% of the population for marijuana use and 1.5% to 2.9% for diagnosed marijuana use disorder.15 More recent data from the results of the 2018 National Survey on Drug Use and Health (NSDUH) found that 15.9% of Americans aged 12 or older use marijuana, higher than percentages from 2002 to 2017.2 It is posited that this trend could be related to a true increase in use; however, changes in social and cultural acceptability as well as legal status play a definite role in increased patient likelihood to admit to usage as well as increased physician likelihood to document cannabis use in the medical record.1,7,15,16 Social and cultural acceptability, however, may also influence physicians not to assign patients with a diagnosis of cannabis use disorder despite patients admitting to its use given its relative normalization in society.7,16 Thus, it would be reasonable to assume that the prevalence of cannabis use disorder in surgical patients has increased in accordance with that among the general population.7 With ongoing state decriminalization and legalization efforts and related public acceptance, this condition is a continually growing consideration for surgeons to take into account perioperatively given the multiorgan side effects of cannabis use.
On a related note, it follows that rates of self-reporting of cannabis use may vary depending on socioeconomic factors, such as employment status, living environment, income, and racial/ethnic disparities. In considering these factors, this study controlled for patient race/ethnicity as well as insurance status, which in and of itself often serves as a marker of many aspects associated with socioeconomic status in the United States (e.g., lower-income individuals with Medicaid, with comparatively lower access to care, and higher-income individuals with private insurance).12,13 Thus, by including race/ethnicity and insurance status in our propensity matched final model, we aimed to control for the major aspects of socioeconomic status while taking care not to over-fit the data.
The present study found that patients with active cannabis use disorder do not have higher rates of postoperative MI compared to patients without cannabis use disorder. This stands in contrast, to an extent, with existing literature regarding the spectrum of detrimental effects of cannabis intake on the cardiovascular system. However, of note, existing human trials are largely limited by their sole administration of tetrahydrocannabinol (THC), the principal active ingredient in cannabis, to test subjects but do not account for other ingredients present in many smoked forms of cannabis, which may have contaminants or other active substances (e.g., “lacing” with tobacco and other substances). Impact on the cardiovascular system is largely mediated by modulation of the autonomic nervous system.17–22 At low or moderate doses, cannabis is found to increase sympathetic nervous system activity resulting in increased heart rate, cardiac output, and blood pressure.7,17–19,22–29 At higher doses, the parasympathetic system is activated resulting in bradycardia and hypotension.17–19,26,27,30 Effects of cannabis on heart rate appear to peak 10 to 30 minutes after smoking; however, the high liposolubility of cannabinoids and subsequent long-lasting accumulation of THC may be associated with sustained tachycardia experienced by patients receiving general anesthesia up to 72 hours after cannabis exposure.7,19,24,27,28,31–33 THC is also reported to cause a wide range of electrocardiogram changes including premature ventricular contractions, atrial fibrillation, atrioventricular block, ventricular tachycardia, ventricular fibrillation, Brugada-like changes, or even asystole.17–19,28,34–41 The most feared cardiovascular complication associated with cannabis use is, of course, acute MI. Previous studies have identified cannabis use as a trigger for acute MI, especially in patients with underlying coronary artery disease.7,17,19,37,42–46 Additionally, given that patients are likely required to cease marijuana usage during inpatient hospitalization, they may develop hypertension and tachycardia secondary to withdrawal.7,47 The supply-demand mismatch in oxygen combined with the synergistic cardiovascular relationship of THC and surgical stress induced hypertension, tachycardia, and increased cardiovascular oxygen demand altogether may predispose patients with cannabis use disorder to higher perioperative risk of MI.7,17,32 Initially, we had found a nearly six-fold rate of MI in the cannabis group (OR 6.23; 95% CI 1.1–159.4, P = 0.034); however, after additionally controlling for concomitant tobacco use in this study, which was far more prevalent in the cannabis group, the rate of MI equalized between cannabis and non-cannabis patients. This suggests that comorbid tobacco use, rather than cannabis itself, may be the primary factor in the higher incidences of associated cardiac ischemia in the literature.
Thromboembolism and Stroke
Additionally, various studies have identified the effects of cannabis consumption on hemostasis. The literature reveals contradictory data with some studies concluding that cannabinoids and their metabolites reduce platelet activation and diminish platelet aggregation as well as platelet count, whereas other studies have found that THC in fact increases platelet activation and creates a prothrombotic environment.17,19,46,48–59 Both effects could have surgical implications as an anticoagulatory effect could lead to difficulty achieving intraoperative blood loss and increased operative blood loss, whereas coagulant effects may predispose patients to various venous thromboembolic events, MI, or ischemic stroke. Marijuana use has been associated with increased rates of ischemic stroke in the literature as well.6,17,19,39,60–65 In addition to thrombotic causes, increased stroke risk has also been attributed to marked blood pressure swings as well as cerebral vasospasm as potential etiologies for cannabis-related cerebrovascular disease.17,19,46,63,66–69 In this study, we found that there was a more than two-fold increase in the associated incidence of thromboembolic events associated with cannabis use, as well as a near three-fold increase in neurologic complications (which includes postoperative stroke), even after controlling for comorbid conditions and concomitant tobacco use, which lends support to those studies suggesting that cannabis may create a prothrombotic environment.
Given that the most common route of cannabis consumption is inhalation via smoking, there is also a profound effect on the respiratory system.17,19 The present study found that patients with cannabis use disorder have a two-fold increased risk of developing respiratory complications postoperatively. This is consistent with the literature which suggests a multitude of potential etiologies regarding the increased respiratory risk profile for those with cannabis use disorder. Previous studies have shown that cannabis smokers have patterns of airway inflammation and bronchial hyperreactivity similar to that of chronic tobacco smokers.70–75 In fact, the bronchial tissue damage caused by three to four marijuana cigarettes has been estimated to be equivalent to that caused by 20 tobacco cigarettes.71 Thus, the increased bronchial tone and risk of bronchospasm after airway manipulation in chronic users pose substantial perioperative risk.76 More immediate preoperative cannabis inhalation has been associated with postoperative airway obstruction secondary to pharyngeal and uvular edema.73,77–81 Additionally, deeper inhalation and longer breath-holding practices involved with smoking cannabis result in blood carboxyhemoglobin levels up to five times those of tobacco smokers, predisposing these patients to potential hypoxic tissue damage.71,82–84 Chronic associated damage to the respiratory tract is associated with an increased rate of respiratory infections, which may, in turn, also explain this study's finding of increased rate of septicemia in this study. These are a variety of mechanisms by which cannabis inhalation can predispose patients to severe postoperative respiratory complications, and in turn, contribute to the drastically increased risk of unfavorable disposition, increased costs and prolonged length of stay among those affected in our study.
Implications for Anesthesiology and Surgical Management
Altogether, these various multiorgan effects of cannabis make surgical patients with cannabis use disorder extremely complex in their management. This is irrespective of the wide variety of known interactions and cross-tolerances between cannabis and many anesthetics or drugs commonly given intraoperatively. Multiple studies have identified cross-tolerances between cannabis and barbiturates, opioids, prostaglandins, and chlorpromazine amongst others.17,19,31,85–88 Given the possibility of potentially lethal interactions, Dickerson et al recommends avoiding anesthesia in any patient with cannabis use within the past 72 hours and Ashton et al recommends avoiding elective operations altogether.31,32,89 The cross-tolerance of cannabis with opioids is notable also in the postoperative period considering postoperative pain is most commonly managed with opioids. Patients with cannabis use disorder are likely given a diagnosis of drug abuse in the health record potentially impacting the willingness of practitioners to offer adequate opioid doses for postoperative pain relief.90,91 Even if these patients receive standard postoperative opioid doses, they may require increased dosing given the cross-tolerance of cannabis with opioids. Studies have found a narcotic requirement of nearly twice that of an average patient for adequate pain control in cannabis users, and this must be given special attention considering the potential complications that may arise from increased opioid dosing.17,19,67,87,92 Thus, there is a significant possibility that patients with cannabis use disorder do not receive adequate pain control. It is well known that inadequately controlled postoperative pain lengthens hospital stays, delays time to first ambulation, impedes physical therapy, increases healthcare costs, and is associated with lower patient satisfaction with outcomes.17,93 The present study found that patients with cannabis use disorders stayed in the hospital for nearly 2 more days, had higher total hospital costs by almost $15,000, and were more likely to be discharged to SNF or rehabilitation facilities and less likely to be discharged to home health care than those without cannabis use disorder. Thus, the complexity of pain management in patients with cannabis use disorders may predispose them to inadequate pain control and subsequently diminished postoperative recovery requiring longer, more expensive hospital stays and requirements for more intensive rehabilitation and care unable to be done at home.
Aside from the previously discussed impacts on cerebrovascular events such as stroke, the literature remains sparse regarding the risks of cannabis use disorder on neurosurgical patients specifically. Behrouz et al94 found that cannabis use is associated with delayed cerebral ischemia and subsequently poor outcomes following aneurysmal subarachnoid hemorrhage. Anesthesiology literature has explored the effect of cannabis use on outcomes of elective procedures and some claim cannabis use to be a complete contraindication to receiving any form of elective surgery given the immense potential for complications with anesthesia.7,17 To date no studies have analyzed the impact of cannabis use on outcomes of any elective neurosurgical procedures. Thus, the present study is the first to explore the impact of cannabis use disorder on outcomes of elective spine surgery.
This study reveals multiple aspects of perioperative care that are extremely complex and difficult in patients with cannabis use disorder. Their high-risk cardiorespiratory profiles combined with specialized anesthetic considerations pre-, intra-, and postoperatively necessitate very unique perioperative management. Although specific interventions may be unknown or unproven in reducing rates of adverse outcomes in these patients, this study serves to highlight an extremely high-risk group of patients in elective spine surgeries. Given that the prevalence of patients the cannabis use disorder will undoubtedly grow due to the evolving legal status and social acceptance of cannabis use, further studies into the optimal perioperative management of these patients are warranted.
This study has several limitations that must be considered. First, as with any retrospective cohort analysis, there may be other potential confounders unable to be adjusted for given the limitations of ICD-9 coding in the Nationwide Inpatient Sample (NIS), and that therefore, the associations found in this study may not necessarily equate to a causative relationship. Similarly, there may be a lack of specificity in the coding of the database as well as the possibility of coding errors or discrepancies given that it is an administrative database. This lack of code specificity manifests most in the exposure definition of the present study. Due to the coding variability among providers, it is impossible to precisely differentiate between users coded with “cannabis dependence” versus those coded “cannabis abuse.” Thus, these two groups of patients were combined into our one exposure group entitled “cannabis use disorder” and allowed us to determine risks and associations perioperative morbidity when undergoing elective spine surgery.
That being said, these codes are unable to account for the degree or duration of cannabis use as they do not account for all cannabis users or even chronic users. Additionally, the coding does not allow us to specify the method of cannabis consumption either. This includes differences and nuances that exist among various prescription cannabinoids (medical cannabis) versus nonprescribed forms of cannabis and cannabis-laced products, as the ICD system is not able to differentiate these forms in its coding. More importantly, the grouping of patients by a diagnosis suggesting a cannabis use disorder naturally excludes recreational users, who may be present in the control group. Thus, the conclusions of this study should not be overgeneralized to all cannabis users, and further prospective studies quantifying cannabis use and postoperative complications are warranted to determine the degree to which dose, frequency and duration of cannabis use affect perioperative complications and management for patients with cannabis use disorder following elective spine surgery.
Chronic cannabis use among patients undergoing spine surgery is associated with higher rates of inpatient neurovascular, thromboembolic, and pulmonary complications, and less favorable overall discharge disposition. The treatment of these patients is also associated with increased length and cost of hospitalization. Patients undergoing these procedures may benefit from a more thorough screen of their social history, particularly in the context of societal stigma associated with cannabis use, and spine surgeons should ensure that patients are adequately informed of associated risks.
- Elective spine surgery patients who abuse cannabis have a higher perioperative morbidity, length of stay, and hospital charges.
- Perioperative respiratory, neurologic, and thromboembolic complications were more prevalent among cannabis abusers.
- These patients also have more unfavorable discharge disposition.
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