Inadvertent Intravascular Administration Research Articles

From disinfectants to antibiotics: Enhanced biosafety of quaternary ammonium compounds by chemical modification

The excessive use of quaternary ammonium compounds (QACs) following the COVID-19 pandemic has raised substantial concerns regarding their biosafety. Overuse of QACs has been associated with chronic biological adverse effects, including genotoxicity or carcinogenicity. In particular, inadvertent intravascular administration or oral ingestion of QACs can lead to fatal acute toxicity. To enhance the biosafety and antimicrobial efficacy of QACs, this study reports a new series of QACs, termed as PACs, with the alkyl chain of benzalkonium substituted by a phthalocyanine moiety. Firstly, the rigid phthalocyanine moiety enhances the selectivity of QACs to bacteria over human cells and reduces alkyl chain’s entropic penalty of binding to bacterial membranes. Furthermore, phthalocyanine neutralizes hemolysis and cytotoxicity of QACs by binding with albumin in plasma. Our experimental results demonstrate that PACs inherit the optical properties of phthalocyanine and validate the broad-spectrum antibacterial activity of PACs in vitro. Moreover, the intravascular administration of the most potent PAC, PAC1a, significantly reduced bacterial burden and ameliorated inflammation level in a bacteria-induced septic mouse model. This study presents a new strategy to improve the antimicrobial efficacy and biosafety of QACs, thus expanding their range of applications to the treatment of systemic infections.

Cardiac arrest after thoracic paravertebral block with ropivacaine in a 6-year-old child

We encountered cardiac arrest induced by 0.375 % ropivacaine 7 ml administered via a catheter for continuous thoracic paravertebral block (TPVB) in a 6-year-old female who underwent pacemaker implantation for sick sinus syndrome (SSS). She was successfully resuscitated with adrenaline and lipid emulsion. Plasma concentration of ropivacaine was 5.2 μg/ml, suggesting intravascular administration of ropivacaine. Inadvertent intravascular administration is a crucial complication of TPVB.

Allergic reaction in the use of primacaine adrenaline.

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA He H, Feng L, Liu H. Letter to the EditorAllergic reaction in the use of primacaine adrenaline. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2015;32(2):134-136. doi:10.5114/pdia.2015.48035. APA He, H., Feng, L., & Liu, H. (2015). Letter to the EditorAllergic reaction in the use of primacaine adrenaline. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 32(2), 134-136. https://doi.org/10.5114/pdia.2015.48035 Chicago He, Hui Xia, Lin Feng, and Hong Chen Liu. 2015. "Letter to the EditorAllergic reaction in the use of primacaine adrenaline". Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii 32 (2): 134-136. doi:10.5114/pdia.2015.48035. Harvard He, H., Feng, L., and Liu, H. (2015). Letter to the EditorAllergic reaction in the use of primacaine adrenaline. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 32(2), pp.134-136. https://doi.org/10.5114/pdia.2015.48035 MLA He, Hui Xia et al. "Letter to the EditorAllergic reaction in the use of primacaine adrenaline." Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, vol. 32, no. 2, 2015, pp. 134-136. doi:10.5114/pdia.2015.48035. Vancouver He H, Feng L, Liu H. Letter to the EditorAllergic reaction in the use of primacaine adrenaline. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2015;32(2):134-136. doi:10.5114/pdia.2015.48035.

Ophthalmologic complications and local anesthesia. Pathophysiology and types of eye complications after intraoral dental anesthesia, and clinical recommendations

The present article reviews the different types of ophthalmologic complications following administration of intraoral local anesthesia. Since the first report by Brain in 1936, case reports about that topic have been published regularly in the literature. However, clinical studies evaluating the incidence of ophthalmologic complications after intraoral local anesthesia are rarely available. Previous data point to a frequency ranging from 0.03% to 0.13%. The most frequently described ophthalmologic complications include diplopia (double vision), ptosis (drooping of upper eyelid), and mydriasis (dilatation of pupil). Disorders that rather affect periorbital structures than the eye directly include facial paralysis and periorbital blanching (angiospasm). Diverse pathophysiologic mechanisms and causes have been reported in the literature, with the inadvertent intravascular administration of the local anesthetic considered the primary reason. The agent as well as the vasopressor is transported retrogradely via arteries or veins to the orbit or to periorbital structures (such as the cavernous sinus) with subsequent anesthesia of nerves and paralysis of muscles distant from the oral cavity. In general the ophthalmologic complications begin shortly after administration of the local anesthesia, and disappear once the local anesthesia has subsided.

Managing Endodontic Patients with Severe Gag Reflex by Glossopharyngeal Nerve Block Technique

IntroductionGagging is a protective reflex, but when the gag reflex becomes abnormally active, it poses a difficulty for the dentist because it hinders all aspects of dental procedures including diagnosis, radiography, and any form of active procedure. MethodsIn this case report, to overcome this difficulty the authors used a glossopharyngeal nerve block technique that is used by anesthetists and otolaryngologists, but its endodontic use has gone previously unreported. ResultsResponse to gag reflex decreases after successful glossopharyngeal nerve block. ConclusionsThe glossopharyngeal nerve block technique is a relatively safe, simple, and easy to master technique as compared with general anesthesia for treating a patient with an exaggerated gag reflex. The glossopharyngeal nerve block technique may be used in dental procedures in patients with an exaggerated gag reflex or when performing procedures in the posterior aspect of the mouth. Due caution should be exercised to prevent inadvertent intravascular administration of local anesthetic when using this procedure.

Ophthalmic complications and local anesthesia. Pathophysiology and types of eye complications after intraoral dental anesthesia, and clinical recommendations

The present article reviews the different types of ophthalmologic complications following administration of intraoral local anesthesia. Since the first report by Brain in 1936, case reports about that topic have been published regularly in the literature. However, clinical studies evaluating the incidence of ophthalmologic complications after intraoral local anesthesia are rarely available. Previous data point to a frequency ranging from 0.03% to 0.13%. The most frequently described ophthalmologic complications include diplopia (double vision), ptosis (drooping of upper eyelid), and mydriasis (dilatation of pupil). Disorders that rather affect periorbital structures than the eye directly include facial paralysis and periorbital blanching (angiospasm). Diverse pathophysiologic mechanisms and causes have been reported in the literature, with the inadvertent intravascular administration of the local anesthetic considered the primary reason. The agent as well as the vasopressor is transported retrogradely via arteries or veins to the orbit or to periorbital structures (such as the cavernous sinus) with subsequent anesthesia of nerves and paralysis of muscles distant from the oral cavity. In general the ophthalmologic complications begin shortly after administration of the local anesthesia, and disappear once the local anesthesia has subsided.

Calculation skills for nurses: Local anaesthetic agents

M clinical scenarios require the administration of local anaesthetic. Local anaesthetics are generally viewed as safe drugs, with a low risk of systemic adverse drug reactions when prescribed and administered correctly (Faccenda and Finucane, 2001). However, if toxicity arises—as a result of exceeding the maximum safe dose (MSD), inappropriate use, or inadvertent intravascular administration—the consequences for the neurological and/or cardiovascular systems can be serious (Cox et al, 2003). The aim of this article is to assist nurse prescribers to administer safe levels of injectable local anaesthetic agents. Allergic reactions are not included, as they are unrelated to the calculation of safe doses. Agents predominantly for dental use and topical agents are also excluded. All local anaesthetics reversibly block nerve conduction at a local level without impeding consciousness. Most local anaesthetics in routine use in the UK are amide compounds (e.g lidocaine and bupivacaine), which undergo hepatic metabolism and predominantly renal excretion (Edgcombe and Hocking, 2006). The speed of onset, potency, and duration of action depend upon the active agent, the percentage concentration and the addition of vasoconstrictors. Vasoconstrictors, such as adrenaline, alter drug kinetics and hence may impact on the permitted dose. They shrink local vasculature and slow the rate of absorption of the anaesthetic into the circulation, prolonging the anaesthetic effect. A temporal decrease in systemic absorption means that toxic concentrations are less likely, and this is reflected in higher MSDs for some agents (Table 1). Formally, there is no change for bupivacaine with adrenaline, to minimise the cardiotoxic risk. Despite this, some sources advise that the MSD can increase to 2.5 mg/kg with adrenaline (Anaesthesia UK, 2009).

Influence of bupivacaine injection dose rate on cardiovascular depression, subsequent hemodynamic course, and related bupivacaine plasma levels in piglets

Systemic local anesthetic (LA) toxicity resulting from inadvertent intravascular injection of LA is a rare but potentially fatal event. Early recognition of intravascular injection and approaches to improve therapeutic safety are required. This study investigated the influence of intravascular injection dose rate of bupivacaine on bupivacaine plasma levels and timing of LA-induced cardiovascular compromise. Forty-five piglets, anesthetized with sevoflurane, were randomized into three groups. Bupivacaine was intravenously infused at a rate of 1, 4, or 16mg/kg/min (groups A, B, and C, respectively) until mean arterial pressure (MAP) dropped to 50% of initial value. Thereafter, bupivacaine infusion was stopped and spontaneous hemodynamic course was observed. Time to MAP50%, amount of bupivacaine infused, bupivacaine plasma level at infusion stop, spontaneous survivors, or time from bupivacaine stop to circulatory arrest were recorded. Median time to MAP50% was 297, 119, and 65s, respectively, in groups A, B, and C (P<0.001). Median corresponding total amounts of bupivacaine infused were 5.0, 7.8, and 17.0mg/kg (P<0.01), and median bupivacaine plasma levels were 53.8, 180.0, and 439.8μmol/l (P<0.001). Five of 15 piglets in group A recovered spontaneously; in groups B and C, all animals died within 120 and 21s, respectively. Higher dose rates of bupivacaine showed much higher plasma bupivacaine levels related to absolute infused dose at MAP50% and were associated with an increased mortality. Slow administration of LA is recommended to allow timely detection and stopping of inadvertent intravascular administration.

Iatrogenic cerebral venous sinus occlusion with flowable topical hemostatic matrix

The use of commercially available topical hemostatic adjuncts has increased the safety profile of surgery as a whole. Cranial surgery has also benefited from the development of numerous agents designed to permit more rapid achievement of hemostasis. Flowable topical hemostatic agents applied via syringe injection are now commonly employed in many neurosurgical procedures, including cranial surgery. Intravascular use of these strongly thrombogenic agents is contraindicated, but in certain settings, inadvertent intravascular administration can occur, resulting in vascular occlusion, thrombosis, and potential dissemination. To date, there have no reports detailing the presence and incidence of this complication. The authors conducted a retrospective review of all cranial surgeries performed at Presbyterian University Hospital by members of the University of Pittsburgh Medical Center's Department of Neurological Surgery between 2007 and 2009. Cases complicated by vascular occlusion due to inadvertent intravascular administration of flowable topical hemostatic matrix (FTHM) were identified and analyzed. Iatrogenic vascular occlusion induced by FTHM was identified in 5 (0.1%) of 3969 cranial surgery cases. None of these events occurred in 3318 supratentorial cases, whereas 5 cases of cerebral venous sinus occlusion occurred in 651 infratentorial cases (0.8%). The risk of accidental vessel occlusion was significantly associated with infratentorial surgery, and all events occurred in the transverse and/or sigmoid sinus. No episodes of inadvertent vascular occlusion occurred during endoscopic surgery. No cases of arterial occlusion were identified. Of the 5 patients with FTHM-related cerebral venous sinus occlusion, none developed long-term neurological sequelae referable to the event. Inadvertent intravascular administration of FTHM is a rare complication associated with cranial surgery that occurs most commonly during infratentorial procedures around the transverse and/or sigmoid sinuses. Modifications in the choice of when to use an FTHM and the method of application may help prevent accidental venous sinus administration.

Lidocaine-induced altered mental status and seizure after hematoma block

Hematoma blocks with lidocaine are routinely utilized in the Emergency Department to allow reduction of Colles’ fractures. Lidocaine toxicity is a potential complication of this procedure. We present a case report of a patient who developed acute mental status changes and generalized seizure immediately following administration of lidocaine during a hematoma block. The rapid onset of seizure development following injection was most likely due to inadvertent intravascular administration.

Treatment of acute lower limb ischemia following the use of the Duett sealing device: report of three cases and review of the literature.

Three cases of local thrombolysis in the treatment of acute lower limb ischemia complicating the utilization of the Duett sealing device are presented. Routine usage of several vascular closure devices after cardiac catheterization and percutaneous coronary intervention (PCI) has been adopted in our institution during the last 3 years (September 1999 to April 2003). The Duett closure device has been used in 420 patients (post-coronary angiography, 359; post-PCI, 61). Three patients (0.7%) demonstrated acute leg ischemia used by inadvertent intravascular administration of the sealing material related to this device. All three were treated successfully by catheter-directed local thromolysis (tissue plasminogen activator 5 mg bolus followed initially by 1 mg/hr and consequently by 0.5-1.0 mg/hr depending upon the development of significant hematoma and lasting for 24 hr). In conclusion, interventional treatment using local thrombolysis should be the first-line treatment in acute lower limb ischemia complicating the utilization of the Duett sealing device.

The efficacy of nicorandil, calcium chloride and nitroglycerin in treatment of ropivacaine-induced cardiotoxicity

Background and objective: The amide-linked local anaesthetics, bupivacaine and ropivacaine, can cause depression of cardiac contractility and dysrhythmias. In a previous study, we observed decreased contractility and ST segment depression following ropivacaine administration in anaesthetized dogs. The efficacy of intravenous (i.v.) and intracoronary nicorandil (30 and 100 μg kg−1), i.v. nitroglycerin (glyceryl trinitrate) (5 μg kg−1) and calcium chloride (1, 2 and 4 mmol) in reversing the cardiotoxic effects of intracoronary ropivacaine were studied following the administration of intracoronary ropivacaine. Methods: Six dogs were studied. The dogs were anaesthetized with i.v. pentobarbital (30 mg kg−1). A left-sided thoracotomy was performed and the left circumflex coronary was cannulated. For each dog, the dose of ropivacaine was identified, which produced measurable cardiotoxicity. In each case, ropivacaine was followed by one of the three resuscitation drugs. The effects of each resuscitation drug on ST segments and left ventricular contractility (dP/dt) produced by ropivacaine alone were compared with those produced by ropivacaine followed by each of the three resuscitation drugs using Fisher's exact test. Results: The doses of ropivacaine required to produce depression of left ventricular dP/dt and ST segments ranged from 1 to 8 mg. Ropivacaine-induced depression of left ventricular contractility (dP/dt) was more rapidly and completely reversed by calcium chloride than by either nitroglycerin or nicorandil (P = 0.008). Conclusions: Calcium chloride may be effective in the treatment of inadvertent intravascular administration of amide local anaesthetic agents.

Ropivacaine

Ropivacaine is a long-acting, enantiomerically pure (S-enantiomer) amide local anaesthetic with a high pKa and low lipid solubility which blocks nerve fibres involved in pain transmission (Adelta and C fibres) to a greater degree than those controlling motor function (Abeta fibres). The drug was less cardiotoxic than equal concentrations of racemic bupivacaine but more so than lidocaine (lignocaine) in vitro and had a significantly higher threshold for CNS toxicity than racemic bupivacaine in healthy volunteers (mean maximum tolerated unbound arterial plasma concentrations were 0.56 and 0.3 mg/L, respectively). Extensive clinical data have shown that epidural ropivacaine 0.2% is effective for the initiation and maintenance of labour analgesia, and provides pain relief after abdominal or orthopaedic surgery especially when given in conjunction with opioids (coadministration with opioids may also allow for lower concentrations of ropivacaine to be used). The drug had efficacy generally similar to that of the same dose of bupivacaine with regard to pain relief but caused less motor blockade at low concentrations. Lumbar epidural administration of 20 to 30ml ropivacaine 0.5% provided anaesthesia of a similar quality to that achieved with bupivacaine 0.5% in women undergoing caesarean section, but the duration of motor blockade was shorter with ropivacaine. For lumbar epidural anaesthesia for lower limb or genitourinary surgery, comparative data suggest that higher concentrations of ropivacaine (0.75 or 1.0%) may be needed to provide the same sensory and motor blockade as bupivacaine 0.5 and 0.75%. In patients about to undergo upper limb surgery, 30 to 40ml ropivacaine 0.5% produced brachial plexus anaesthesia broadly similar to that achieved with equivalent volumes of bupivacaine 0.5%, although the time to onset of sensory block tended to be faster and the duration of motor block shorter with ropivacaine. Ropivacaine had an adverse event profile similar to that of bupivacaine in clinical trials. Several cases of CNS toxicity have been reported after inadvertent intravascular administration of ropivacaine, but only 1 case of cardiovascular toxicity has been reported to date. The outcome of these inadvertent intravascular administrations was favourable. Ropivacaine is a well tolerated regional anaesthetic with an efficacy broadly similar to that of bupivacaine. However, it may be a preferred option because of its reduced CNS and cardiotoxic potential and its lower propensity for motor block.

Need for Precise Diagnosis prior to Epidural Steroids

To the Editor:—I enjoyed the article by Dr. Stephen Abram. I would like to point out that an additional dimension to the discussion of effectiveness of epidural steroids can be found by applying the “numbers needed to treat” approach, as outlined in the excellent resource regarding the topic of pain relief using an evidence-based medicine approach published recently by McQuay and Moore. An additional important potential complication of administration of Depo corticosteroids has come to my attention, and I believe that it should be mentioned, particularly with reference to Depo-Medrol (Pharmacia & Upjohn, Peapack, NJ). Inadvertent intravascular administration of Depo corticosteroid, producing occlusion of small end arteries, was reported to result in visual defects in one case. I am aware of a further case that involved a suboccipital nerve block, and the patient experienced ongoing hearing loss. Both of these cases were associated with administration of Depo corticosteroid in the head and neck area, with the potential for retrograde flow into end arteries. The risk of Depo corticosteroid reaching end arteries from epidural administration will presumably be smaller, although one must have some concern about particulate matter reaching small radicles of spinal arteries. Michael J. Cousins, M.D. Professor and Head Department of Anaesthesia and Pain Management University of Sydney Royal North Shore Hospital St. Leonards, New South Wales Australia mcousins@doh.health.nsw.gov.au

Safety of direct myocardial administration of an adenovirus vector encoding vascular endothelial growth factor 121.

A gene therapy strategy involving direct myocardial administration of an adenovirus (Ad) vector encoding the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) has been shown to be capable of "biological revascularization" of ischemic myocardium in an established porcine model [Mack, C.A. (1998). J. Thorac. Cardiovasc. Surg. 115, 168-177]. The present study evaluates the local and systemic safety of this therapy in this porcine ischemia model and in normal mice. Myocardial ischemia was induced in Yorkshire swine with an ameroid constrictor 21 days prior to vector administration. Ad(GV)VEGF121.10 (10(9) or 10(10) PFU), Ad5 wild type (10(9) PFU), AdNull (control vector with no transgene; 10(9) PFU), saline, or no injection (naive) was administered in 10 sites in the ischemic, circumflex distribution of the myocardium. Toxicity was assessed by survival, serial echocardiography, blood analyses, and myocardial and liver histology at 3 and 28 days after vector administration. All pigs survived to sacrifice, except for one animal in the Ad(GV)VEGF121.10 (10(10) PFU) group, which died as a result of oversedation. Echocardiograms of Ad(GV)VEGF121.10-treated pigs demonstrated no differences in pericardial effusion, mitral valve regurgitation, or regional wall motion compared with control pigs. Intramyocardial administration of Ad(GV)VEGF121.10 included only minimal myocardial inflammation and necrosis, and no hepatic inflammation or necrosis. Only a mild elevation of the white blood cell count was encountered on day 3, which was transient and self-limited in the Ad(GV)VEGF121.10 group as compared with the saline-treated animals. As a measure of inadvertent intravascular administration of vector, normal C57/BL6 mice received intravenous Ad(GV)VEGF121.10 (10(4), 10(6), 5 x 10(7), or 10(9) PFU), AdNull (5 x 10(7) or 10(9) PFU), or saline. Toxicity was assessed by survival, blood analyses, and organ histology at 3 and 7 days after vector administration. A separate group of C57/BL6 mice received intravenous AdmVEGF164 (Ad vector encoding the murine VEGF164 cDNA), Ad(GV)VEGF121.10, AdNull (10(8) PFU each group), or saline to assess duration of expression and safety of a homologous transgene. All mice survived to sacrifice except for 40% of the mice in the highest (10(9) PFU; a dose more than 10(3)-fold higher by body weight than the efficacious dose in pigs) Ad(GV)VEGF121.10 dose group, which died on days 5-6 after vector administration. The only differences seen in the blood analyses between treated and control mice were in the very high Ad(GV)VEGF121.10 dose group (10(9) PFU), which demonstrated an anemia as well as an increase in alkaline phosphatase when compared with all other treatment groups. Hepatic VEGF levels by ELISA in AdmVEGF164-treated mice did not persist beyond 14 days after vector administration, suggesting that persistent expression of a homologous VEGF gene transferred with an Ad vector is not a significant safety risk. Although this is not a chronic toxicity study, these data demonstrate the safety of direct myocardial administration of Ad(GV)VEGF121.10, and support the potential use of this strategy to treat human myocardial ischemia.