Cardiac standstill and neurosurgery

A much-needed collaboration for complicated vascular procedures

Abstract

Complex intracranial aneurysm (ICA), large arteriovenous malformations and skull base tumours require absolute clean operative field and can be a battle of nerve testing at time due to torrential bleed. As such, there are various ways to reduce blood loss; however, maintaining cerebral perfusion during bleeding is a challenge. Currently, adenosine, hypothermia with cardiopulmonary bypass and rapid ventricular pacing (RVP) are options adopted at various places. Which one to choose may be a difficult preposition as there are several factors in its determinacy. This systematic review conforming to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines evaluated 52 full-text articles for 2000–2022. A search of PubMed was done with keywords adenosine OR, hypothermia, OR RVP, OR cardiac stand still and ICA [All Fields]. Case reports and only abstracts were excluded. After exclusions, 26 articles were analysed. The relevant information for each modality has been tabulated. Adenosine produces short asystole as compared to RVP. Adenosine can be repeated if need arises. For hypothermia and RVP, one would need a good set-up with intense monitoring and complex logistics. There can be many complex situations where neurosurgeons may still need any of the above methods to choose for variable reasons or indications. Choosing any of the above methods is largely guided by individual set-ups; however, the use of adenosine seems to be simple and easy.

INTRODUCTION

Neurosurgery has passed through several tough terrains to establish itself as a safe branch of surgery which requires utmost dexterity. Unlike other parts of body, bleeding brain is an unforgiving organ which has limited scope to adjust and accommodate haematoma formation.

The gateway of clean and successful neurosurgery hinges upon minimal blood loss during surgery so that the fields are clearly visible. Any excessive bleeding can create panic even to experts, and it soon results in brain oedema and herniations which can add to more problems. At times, torrential intra-operative bleeding and inability to localize the exact site of bleed compels the neurosurgeon to apply clips blindly. Additionally, inadvertent coagulation and clipping can result in infarctions of brain tissue.

Some of the conditions of brain which can result in massive bleed are aneurysm, arteriovenous malformations (AVM), skull base tumours and certain other tumours. Site of lesions also plays a vital role in controlling bleeding, e.g., cavernous sinus and basilar artery.

In order to have a clean field during surgery, several options are available, e.g., pre-operative embolisation, exposure of common carotid artery and temporary clamp of carotid artery in neck and intraoperative hypotension.

Cardiac standstill is a method which can produce a near cardiac asystole so as to stop the circulation of blood to facilitate a surgeon to perform the required steps as indicated. It is a very challenging technique which has to keep a balance of no flow to the site of surgery as well as to prevent cerebral ischaemia. Intraoperative hypothermia, cardiac bypass machines, intraoperative adenosine and rapid ventricular pacing (RVP) are some of the methods being practiced to reduce bleeding and facilitate clipping.

The review article is to analyse the role of these techniques and to understand the current applications and merit of each for the larger benefit of patients. It also focuses on the merit of each such modality and the ease and complexity of each method.

HISTORICAL PERSPECTIVES

Bleeding from vascular lesions, particularly during aneurysm surgery, has been a portal of resistance for successful clipping.[¹] Since the first surgery for aneurysm by Norman McComish Dott by the method of ligating the carotid artery in 1931, there have been several advances.[²] Harry Botterell and William Lougheed used hypothermia in 1940–1950 on dogs.[¹³] Human application for aneurysm was utilised by William Sweet.[¹] The first case of circulatory arrest was used in 1955 for large arteriovenous malformations. Surgical clipping along with hypothermia has been reported in a large series by Toronto General hospital in 1958. Later on, Charles Drake at Western Ontario used a combination of hypothermia and cardiopulmonary bypass in a series of 10 patients in the year 1963.[⁴] In addition, open chest circulatory arrest using Drew techniques gave impetus to vascular neurosurgery using deep hypothermia (12°C–14°C or 53.6°F–57.4°F).[⁵] The use of ventricular fibrillation (VF) by direct electrical stimulation of left ventricle was described by AaaronGissen which further added 4 min of circulatory arrest.[⁶] Open chest application of alternate current directly to heart-induced VF was later adopted by many. In 1988, Robert Spetzler from Barrow Neurological Institute used barbiturate in addition to hypothermia and complete circulatory arrest for neurological protection.[⁷]

Adenosine application for cardiac standstill emerged in 1999 by Michael Groff from Mr. Sinai School of Medicine.[^8,9] Later on, several series were reported for the benefits of adenosine by various authors.

MATERIALS AND METHODS

As per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search was made in PubMed for the recent articles of full-text review published between 2000 and 2022 using keywords: adenosine OR, hypothermia, OR Rapid ventricular pacing, OR cardiac stand still and intracranial aneurysm [All Fields]. Abstracts alone and where full-text articles could not be retrieved were excluded.

A total of 52 articles were retrieved for each pairing. Intracranial aneurysm (ICA) and adenosine revealed 13, ICA and RVP 3, ICA and hypothermia 28 and ICA and cardiopulmonary bypass 8 articles. Duplicate and unrelated articles were excluded (n = 26). Final analysis was performed on 26 relevant full-text review articles [Figure 1].

Figure 1: PRISMA Flow chart for search of articles and analysis. (ICA –Intracranial Aneurysm, RVP-Rapid Ventricular Pacing, CPB- Cardio-Pulmonary Bypass)

The summary of various articles discussed in PRISMA has been arranged, and the highlights are discussed in [Table 1].

Table 1: Summary of selected articles reviewed

The review found three common modalities to assist a surgeon in complex situation of clipping of ICA. RVP, hypothermia with cardiac bypass and adenosine have been used rather sparingly. Each modality has its benefit and limitation; therefore, the use of any one of the above warrants a complete understanding of concept and utilisation. Various authors have recommended various aspects, and therefore, there is no consensus which one to choose.

ADENOSINE STANDSTILL

Systemic use of adenosine has been reported in several reports.[^{35,36,37,38,39,40,41,42,43,44,45,46,47,48}] Because of its availability and easy to use, it has been established now at several neurosurgical units. One of it major advantages is its rapid action and short half-life (<10 secs).[^35,36]

It acts both on heart and peripheral vessels on different receptors.[^37,38] Primary action is on sinoatrial node where it binds with A1 receptors and decreases heart rate. In addition, it also acts on AV node producing negative chronotropic effect, produces vasodilatation and thus reduces blood pressure. It does not cause rebound hypertension that is a major advantage in neurosurgery.[^39,40,41] Therefore, multiple injections can be given during the procedure. It takes about 30 s to induce asystole. The duration of asystole is dose dependent, but it varies amongst patients. Most authors record a starting dose of 6 mg as dose test.[^35,42] In some cases, a higher dose of 60mg may be needed. Adenosine produces asystole of 20–30 s and hence dose repetition may be required. In the event of intraoperative rupture, incremental dose administration cannot be used. Some authors have proposed bolus 0.4 mg/kg ideal body weight with a median dose of 30 mg to obtain to produce a median of 20 s asystole (5–30s).[^35,36] It is recommended to keep external defibrillator ready in all cases to manage any untoward incidence of unstable atrial fibrillation. Meling et al. have used it in intraoperative ruptures, to reduce the chances of dangerous drilling of clinoid process.[⁴³] The role of adenosine has been documented to make the aneurysm soft, which helps in clipping a wide necked and partially thrombosed aneurysm. Almost all locations of aneurysm have been clipped using adenosine with safety, mostly in unruptured aneurysms.[^44,45,46,47]

Prolonged hypotension is one of the major concerns with adenosine, the period of which may last for about 30 min. It is also associated with profound reduction in systemic vascular resistance.[⁴⁸] Restoration of hypotension after cessation of adenosine occurs within 3 minutes; however, it may be prolonged with repeated administration.[^35,36]

Sollevi et al. have used continuous infusion with effect coming in 1–2 min and restored after stopping within 1–5 min.[⁴⁹] The mean arterial pressure (MAP) decreased to 46 mmHg within 1 min. Some of the relative contraindications are MI, wherein adenosine can produce regional ischaemia or previous heart blocks. Other relative contraindications include gout and bronchial asthma, as they may induce bronchospasm.

RAPID VENTRICULAR PACING

RVP is a method which produces virtual asystole and transient hypotension. In this method, a pacemaker electrode is placed in right ventricle via internal jugular vein.

Tachycardia is induced which impedes ventricular filling and simultaneously reduces ventricular contraction. It results in reduced stroke volume and blood pressure without actually producing cardiac arrest or asystole. The procedure begins to keep heart rate of 150/min and eventually it is gradually increased to induce a MAP of under 50 mmHg. It can be combined with regular methods of intraoperative hypotension. After cessation of RVP, systolic blood pressure returns back to normal immediately, and contrary to adenosine, there is no prolonged hypotension.[²³]

Unlike adenosine which can result in MAP of 0, the hypotension with RVP can be sustained around 40 mmHg for a longer duration and thus has a lesser risk of microembolism and infarct.

Although several episodes of RVP can be applied, most literature have used an average of 3 cycles of pacing.[²⁴] Indication of pacing is largely to produce the slackness of aneurysm for clipping. Pacing is usually indicated when the sizes of aneurysm are large to giant. The majority of aneurysms are wide neck and located in intracavernous region.[⁵⁰]

Reported complications are tachyarrhythmias (VF and atrial fibrillation) reversible with cardioversion. A small rise in troponin I levels is also reported. Rare procedural complications are cardiac tamponade, cardiac perforation, myocardial infarction and pneumothorax. Contraindications include prior myocardial infarction and severe left ventricular dysfunction.[⁵¹]

HYPOTHERMIA AND CARDIOPULMONARY BYPASS

Hypothermia has been extensively used to treat neurosurgical conditions such as head injury. Its role in managing complex aneurysm and carotid-cavernous fistula has been sparingly used. It reduces the metabolic demand of brain and hence increases tolerance for tissue hypoxia during blood loss.

TECHNICAL ASPECTS OF CARDIOPULMONARY BYPASS AND HYPOTHERMIA

Selection of suitable case is definitely challenging and necessitates close-knit teamwork. Cardiovascular surgeons, neurosurgeons, anaesthesiologists and perfusionists have to work in close harmony for optimal conditions in the surgical field.

The technique involves placing creating extracorporeal circulation usually by placing two cannulas, one each in femoral artery and vein [Figure 2]a, [Figure 2b and Figure 3]. This can also be achieved by sternotomy and direct cannulation of aorta and right atrium.

Figure 2: Line diagram explaining cardiopulmonary bypass via femoral route

Figure 3: (a) Exposed femoral artery and vein in an adult, (b) Cannulated artery and vein for bypass

After assessing cardiovascular, pulmonary, renal and hepatic systems, it is essential to rule out peripheral vascular disease also. Oesophageal stricture, stenosis, surgery or trauma precludes the use of trans-oesophageal echocardiography (TEE). Baseline blood investigations, electrocardiography, chest X-ray and echocardiography (to rule out associated vascular anomaly, especially aortic valve pathology) are mandatory. Large-bore 16G intravenous cannula is secured and invasive arterial line is inserted under local anaesthesia. Standard general anaesthesia technique is used, keeping in mind suppression of haemodynamic response to laryngoscopy. The American Society of Anesthesiologists monitoring is instituted and additionally cerebral monitoring (bispectral index [BIS], near-infrared spectroscopy, etc.) is desirable/recommended. Central venous line is usually placed in right internal jugular vein. Some authors have also described the use of Swan-Ganz, P-A catheters. A mixture of air–oxygen is preferred for ventilation. Arterial blood gas (ABG) sample is analysed hourly for optimising ventilation and oxygenation. TEE probe is inserted and cardiac chambers and valves are assessed. Ejection fraction is documented, and associated lesions or pulmonary arterial hypertension if present are assessed for severity. The probe generally remainsin situfor the entire procedure. It helps in guiding cannula positions in close chest cardiopulmonary bypass. It is essential to attach sticky defibrillator pads on both sides of chest, connected to defibrillator at all times.

Following this, the patient is positioned for craniotomy as per neurosurgeons' requirement. In addition, chest and groin are also painted and draped, so that they are accessible for CPB. Depth of anaesthesia is ensured, and antibiotics and mannitol (0.5–1 g) are administered. Temperature, BIS, ABG and baseline ACT are recorded and documented. The neurosurgeon again assesses the aneurysm after craniotomy and gives a final nod whether to proceed for cardiopulmonary bypass. The most common technique is femorofemoral bypass.[⁵²] CPB can be established by sternotomy and direct cannulation of aorta and right sternum, but in cases where open heart/chest surgery is not required, sternotomy should not be performed. In such cases, femorofemoral bypass is a preferred technique [Figure 2], though it is also popular for minimally invasive and redo cardiac surgeries.

TECHNIQUE FOR FEMORAL CANNULATION

After exposing the groin area, under all aseptic precautions and adequately cleaning the area, fine surgical dissection is done to expose femoral vessels. Then, unfractionated heparin 300–400U/kg is administered. After administration of heparin, femoral artery and veins are cannulated [Figure 3a and Figure 3b]. ACT is measured after 3 min, and once ACT is >480 s, the patient can be safely taken on heart–lung machine [Figure 4]. Femoral venous cannula is advanced till right atrium under TEE guidance. In general, anaesthesia drugs such as fentanyl, rocuronium/pancuronium and midazolam are administered via pump and heparin in half dose is repeated hourly. Thiopentone or propofol infusions are administered to achieve electroencephalography (EEG) burst suppression till the time the patient goes on CPB and hypothermia is achieved. The cerebral rate of metabolism decreases by 7% for every 1°C fall in temperature.[⁵³]

Figure 4: Image depicting cardiopulmonary bypass via femoral route

Once the CPB is established, and optimal flows are achieved, MAP >50 mg (flow depends on BSA) cooling is initiated by an extracorporeal heat exchanger. Cooling should be done slowly and once target temperature is reached, it is maintained. Mild hypothermia refers to temperature of 32°C–35°C, moderate hypothermia is 28°C–32°C and deep hypothermia is <28°C. In general, moderate hypothermia is advocated on CPB. However, at times, deep hypothermic circulatory arrest (DHCA) is required for giant AVM and aneurysms.[⁵⁴]

The surgeon exposes the surgical site and assesses the aneurysm once again. After confirming with a neurosurgeon, cardioplegia solution is administered to achieve cardiac standstill by the perfusionist, eventually leading to cerebral vascular relaxation. Such manoeuvres produce the slackness of aneurysm. Subsequently, aneurysm can be assessed with ease and the neurosurgeon can comprehend the anatomical complexities of aneurysm and proceed for clipping if possible. If there are issues with identification, flows are reverted and ICG may be performed in special circumstances. If the surgeon thinks vascularity and identification of collaterals is difficult, this is the time to decide if DHCA is required. If DHCA is planned, cerebroprotective agents are administered through CPB machine. The temperature monitoring site recommended is tympanic probe as it truly reflects brain temperature. The CPB time reported in the literature is 160 (117–215) min. However, the aim is to keep the duration of DHCA as minimal as possible, and many studies elaborate 30 min (15–45) to be safe and neurological complications are seen beyond 40–60 min.[^53,55] Besides hypothermia, other neuroprotective strategies are also important such as pharmacological agents, surface head cooling, glucose control, haemodilution and acid–base management.

Once surgical clipping/procedure has been completed, flows are established and the surgeon evaluates the surgical site for haemostasis. If the surgeon is confident that there is no bleeding, rewarming is initiated. Nitroglycerin infusion at low dose may be started to achieve uniform rewarming. Once cardiac activity is gained and electrolytes, ABG and haemodynamics are acceptable, the patient is weaned off cardiopulmonary bypass. Sometimes, minute doses of inotropes may be required to counter the efforts of cardioplegia. Hypothermia and rewarming are associated with rhythm disturbances; therefore, shock may be required in cases of refractory VF or pulseless ventricular tachycardia. Heparin is neutralised with almost equivalent dose of protamine. ACT is again measured and <140 s is considered safe.

It requires a proper infrastructure and set-up which generally exist in all cardiac operation theatres. Intra-operative monitoring with Electo-Encephalography (EEG), Somato-Sensory Evoked Potential (SSEP) and Brainstem Evoked Response Audiometry (BERA).

Lawton et al. studied 60 patients over a span of 12 years, where majority of posterior circulation aneurysms were managed successfully with hypothermic circulatory arrest.[⁵⁶] Various authors have found DHCA to be quite helpful in complex and giant ICA s including basilar artery aneurysms.[^56,57,58,59]

Hypothermia can be of immense use in large and giant aneurysm which currently is viewed as a challenging task. Surgery for complex aneurysm and intracranial bypass procedures are some useful indications for hypothermia and cardiac standstill. Although DHCA confers many surgical advantages, still issues such as coagulopathy, cerebral microembolism, increased plasma viscosity and erythrocyte rigidity, metabolic acidosis, hyperglycaemia and altered drug metabolism must be managed simultaneously.[⁵³] Some of the other complications due to hypothermia include sepsis, myocardial infarction, transfusion-related issues and pulmonary embolism. Mortality related to technique is reported 8%–13%, which may be related to subarachnoid haemorrhage itself.[⁵⁶]

In the current scenario, exclusive indications for DHCA practically include complex posterior circulation and giant aneurysms not amenable to be treated using conventional techniques or that recur after endovascular coiling. Therefore, inspite of decreasing trend for the use of DHCA because of newer technology-driven endovascular methods, it still remains in the armamentarium for managing complex vascular neurosurgery. However, DHCA requires complex infrastructure and a multidisciplinary expert team for optimal management.

After having discussed the existing techniques, all the methods have been analysed detailing on uses, techniques, doses, advantages and disadvantages, as tabulated in [Table 2].

Table 2: Advantages and disadvantages of various methods for cardiac standstill

CONCLUSIONS

Several ICAs, because of size, location and complexity, mandate a surgical approach. Despite technical assistance and advanced techniques, surgical management of ICA becomes a nightmare some time, more so when endovascular options are also difficult for a particular case.

Various authors have described adenosine, RVP and CPB with hypothermia for the management of such complex and difficult situations. Each one has its merit and limitation; hence, there is no consensus to use only a particular method. Whereas hypothermia and cardiac standstill and RVP seem a reasonable option, it requires hybrid theatre, infrastructure and a dedicated team. In comparison, adenosine seems to be simpler and safer modality to choose in limited resources.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.