Sepsis and septic shock

Definitions

Systemic inflammatory response syndrome (SIRS)—Two or more of the following, due to either an infectious or a noninfectious etiology:

• Temperature >38⁰C or >36⁰C
• Respiratory rate >24 breaths/ min
• Heart rate >90 beats/ min
• WBC count >12,000/uL or <4000/uL, or >10% bands

Sepsis—SIRS witha proven or suspected microbial etiology

Severe sepsis—Sepsis withone or more signs of organ dysfunction

Septic shock—Sepsis witharterial blood pressure<90 mmHg or 40 mmHg below pt’s normal blood pressure for at least 1 hdespite fluid resuscitation

Etiology

• Blood cultures are positive in 20–40% of sepsis cases and in 40–70% of septic shock cases. Of cases with positive blood cultures,-40% are due to gram-positive bacteria, 35% to gram-negative bacteria, and 7% to fungi.

• Any class of microorganism can cause severe sepsis.

• A significant proportion of cases have negative microbiologic data.

Epidemiology and Risk Factors

The incidence of severe sepsis and septic shock is increasing in the United States, with >300,000 cases each year. Two-thirds of cases occur in pts hospitalized for other reasons. Sepsis is a contributing factor in >200,000 deaths eachyear in the United States.

The higher incidence of sepsis is due to the aging of the population, longer survival of pts withch ronic diseases, medical treatments (e.g., with steroids or antibiotics), and invasive procedures (e.g., catheter placement). Gram-negative sepsis is associated withunderlying diabetes mellitus, lymphoproliferative disorders, cirrhosis of the liver, burns, neutropenia, and indwelling urinary cathe ters. Gram-positive sepsis is associated withindwelling mechanical devices and intravascular catheters, IV drug use, and burns. Fungal sepsis is associated with neutropenia and broad-spectrum antimicrobial therapy.

Pathogenesis and Pathology

Local and Systemic Host Responses

• Recognition of microbial molecules by tissue phagocytes triggers production and release of cytokines and other mediators that increase blood flow to the infected site, enhance the permeability of local blood vessels, attract neutrophils to the infected site, and elicit pain.

• Through intravascular thrombosis (the hallmark of the local immune response), the body attempts to wall off invading microbes and prevent the spread of infection and inflammation. Key features of the systemic immune response include intravascular fibrin deposition, thrombosis, and DIC; the underlying mechanisms are the activation of intrinsic and extrinsic clotting pathways, impaired function of the protein C–protein S inhibitory pathway, depletion of antithrombin and protein C, and prevention of fibrinolysis by increased plasma levels of plasminogen activator inhibitor 1.

Organ Dysfunction and Shock

• Endothelial injury: Widespread endothelial injury is believed to be the major mechanism for multiorgan dysfunction.

• Septic shock: The hallmark is a decrease in peripheral vascular resistance despite increased levels of vasopressor catecholamines. Cardiac output and blood flow to peripheral tissues increase, and oxygen utilization by these tissues is greatly impaired.

Clinical Features

• Hyperventilation
• Encephalopathy (disorientation, confusion)
• Hypotension
• DIC, acrocyanosis, ischemic necrosis of peripheral tissues (e.g., digits)
• Skin: hemorrhagic lesions, bullae, cellulitis. Skin lesions may suggest specific pathogens—e.g., petechiae and purpura with Neisseria meningitidis, ecthyma gangrenosum in neutropenic pts with Pseudomonas aeruginosa.
• Gastrointestinal: nausea, vomiting, diarrhea, ileus, cholestatic jaundice
• Hypoxemia: ventilation-perfusion mismatchand increased alveolar capillary permeability withincreased pulmonary water content

Major Complications

• Cardiopulmonary manifestations:

Acute respiratory distress syndrome (progressive diffuse pulmonary infiltrates and arterial hypoxemia) develops in -50% of pts withsevere sepsis or septic shock.

Hypotension: Normal or increased cardiac output and decreased systemic vascular resistance distinguish septic shock from cardiogenic or hypovolemic shock.

Myocardial function is depressed withdecreased ejection fraction.

• Renal manifestations: oliguria, azotemia, proteinuria, renal failure due to acute tubular necrosis

• Coagulation: thrombocytopenia in 10–30% of pts. With DIC, platelet counts usually fall below 50,000/uL.

• Neurologic manifestations: polyneuropathy with distal motor weakness in prolonged sepsis

Laboratory Findings

• Leukocytosis with a left shift, thrombocytopenia

• Prolonged thrombin time, decreased fibrinogen, presence of D-dimers, suggestive of DIC

• Hyperbilirubinemia, increase in hepatic aminotransferases, azotemia, proteinuria

• Metabolic acidosis, elevated anion gap, elevated lactate levels, hypoxemia

Diagnosis

Definitive diagnosis requires isolation of the microorganism from blood or a local site of infection. Culture of infected cutaneous lesions may help establish the diagnosis. Lacking a microbiologic diagnosis, the diagnosis is made on clinical grounds.

Treatment

1. Antibiotic treatment

2. Removal or drainage of a focal source of infection

·         Remove indwelling intravascular catheters and send tips for quantitative culture; replace Foley and other drainage catheters.

·         Rule out sinusitis in pts withnasal intubation.

·         Perform CT or MRI to rule out occult disease or abscess.

3. Hemodynamic, respiratory, and metabolic support

    a. Maintain intravascular volume withIV fluids. Initiate treatment with 1–2 L of normal saline administered over 1–2 h, keeping pulmonary capillary wedge pressure at 12–16 mmHg or central venous pressure at 8–12 cmH2O, urine output at >0.5 mL/kg per hour, mean arterial blood pressure at >65 mmHg, and cardiac index at >4 (L/min)/m2. Add inotropic and vasopressor therapy if needed. Maintain central venous O2 saturation at _70%, using dobutamine if necessary.

    b. Maintain oxygenation withventilator support as indicated.

    c. Monitor for adrenal insufficiency or reduced adrenal reserve. Pts witha plasma cortisol response of <9 ug/dL to an ACTH challenge may have improved survival if hydrocortisone (50 mg q6h IV) and 9-alpha fludrocortisone (50 ug/d via nasogastric tube) are administered for 7 days.

4. Other treatments (investigational): Antiendotoxin, anti-inflammatory, and anticoagulant drugs are being studied in severe sepsis treatment. The anticoagulant recombinant activated protein C (aPC), given as a constant infusion of 24 ug/kg per hour for 96 h, has been approved for treatment of severe sepsis or septic shock in pts with APACHE II scores of >25 preceding aPC infusion and low risk of hemorrhagic complications. The long-term impact of aPC is uncertain, and long-term survival data are not yet available. Other agents have not improved outcome in clinical trials.

Shock Algorithm Guidelines  

Prognosis

In all, 20–35% of pts withsevere sepsis and 40–60% of pts with septic shock die within 30 days, and further deaths occur within the first 6 months. The severity of underlying disease most strongly influences the risk of dying.

Prevention

In the United States, most episodes of severe sepsis and septic shock are complications of nosocomial infections. Thus the incidence of sepsis would be affected by measures to reduce those infections (e.g., limiting the use and duration

Concept of Neutral Zone

Definition

‘The neutral zone is that area in the potential denture space where the forces of tongue pressing outward are neutralized by the forces of the cheeks and lips pressing inward’.

Since these forces are developed through muscular contraction during the various functions of chewing, speaking, and swallowing, they vary in magnitude and direction in different individuals.

The Potential ‘Denture Space’

The central thesis of the neutral zone approach to complete dentures is ‘to locate that area in the edentulous mouth where the teeth should be positioned so that the forces exerted by the muscles will tend to stabilize the denture rather than unseat it’.

The soft tissues that form the internal and external boundaries of the denture space exert forces which generally influence the stability of the dentures.

Importance of Neutral Zone

During childhood, the teeth erupt under the influence of muscular environment created by forces exerted by tongue, cheeks and lips, in addition to the genetic factor. These forces has a definite influence upon the position of the erupted teeth, the resultant arch form, and the occlusion.

Generally, muscular activity and habits which develop during childhood continue through life and after the loss of teeth, it is important that the artificial teeth be placed in the arch form compatible with these muscular forces.

As the area of the impression surface decreases (due to alveolar ridge resorption), less influence it has on the denture retention and stability.

Consequently, retention and stability become more dependent on the correct positioning of the teeth and the contours of the external or polished surfaces of the dentures.

Therefore, these surfaces should be so contoured that the horizontally directed forces applied by the peri -denture muscles should act to seat the denture.

The Neutral-Zone Philosophy

is based upon the concept that for each individual, there exists within the denture space a specific area where the function of the musculature will not unseat the denture & where forces generated by the tongue are neutralized by the forces generated by lips and cheeks.

The artificial teeth should not be placed on the crest of the ridge or buccally or lingually to it – rather these should be placed as dictated by the musculature.

The objectives achieved by this approach are,

                a) the teeth will not interfere with the normal muscle function, &

                b) the forces generated by these muscles against the denture, especially for the resorbed lower ridge, are more favorable for stability & retention.

Muscles involved in the ‘Neutral Zone’

The musculature of the denture space can be divided into two groups,

                1. those muscles which primarily dislocate the denture during activity (Dislocating muscles),

                2. those muscles that fix the denture by muscular pressure on the polished surfaces (Fixing muscles).

These can then be further divided according to their location on the vestibular (labial & buccal) side or lingual side of the dentures.

Dislocating muscles

                Vestibular:

                                Masseter

                                Mentalis

                                Incisive Labii Infer.

                Lingual:

                                Medial Pterygoid

                                Palatoglossus

                                Styloglossus

                                Mylohyoid

Fixing muscles

                Vestibular:

                                Buccinator

                                Orbicularis oris

                Lingual:

                                Genioglossus

                                Lingual longitudinal

                                Lingual vertical

                                Lingual transverse

Technique for  the  Location  of  Neutral  Zone

A number of variations of the basic technique have been reported in the literature. However, with all these techniques of neutral zone approach, the usual sequence of complete denture construction is somewhat reversed.

1. Individual trays are constructed and adjusted carefully in the mouth so that these are stable on opening the mouth, speaking, and swallowing.

2. Modeling compound is used to fabricate occlusion rims.

3. These rims are then molded intra orally according to the muscle function – recording of neutral zone.

4.  Establishing the tentative OVD and CR.

5.  Obtain the final impression with the closed mouth technique.

6.  Final determination of the OVD and CR.

7.  Pouring the casts, forming the plaster index, their articulation, and Set-up of the teeth.

8.  Wax try-in of the dentures and verification of the tooth position intra-orally.

9.  Finally, obtaining the impression of the polished surfaces and establishing their contours in the wax-up.

 

Recording the Neutral Zone

 

Jaw relation records & reference lines

Plaster index fabrication and tooth arrangement

Tooth arrangement & initial wax-up for the soft tissue contours – lingual index removed

Tooth arrangement in the Neutral Zone Buccal Plaster indices are being removed

Waxed complete dentures Intra oral Try – in

Recording Neutral Zone - Soft tissue Contours

Application of Vaseline before adding impression material  

Impression material is evenly applied on the buccal and lingual surfaces of the waxed-up dentures

Patient performs oral functions including chewing to determine the thickness, contour and shape of the polished surfaces

Carefully inspect the impression of the polished surfaces including the palatal area – for complete coverage by the impression material

The material flown over the tooth surfaces must be removed carefully with a carver

The Finished Complete Dentures based on the Neutral Zone Concept

Recording Neutral Zone for a Single Complete Denture

Occlusal stops established intra-orally and retentive wire added to the special tray

Slow setting medium viscosity silicone impression material is coated on all the surfaces.

After inserting the tray, patient is advised to smile, swallow and to produce vowels, ‘ooh, ah’, until the material is set.

Denture space Impression after removal from the mouth

Its appearance is totally un-conventional. Any evidence of large areas of air entrapment, insufficient or excessive volume of impression material, or tray showing through necessitate re-taking the impression.

The Poured Denture space Impression-Four matrices are required to record the buccal, labial, lingual & ridge contours

The impression seated on the ridge matrix (with the buccal, labial and lingual matrices removed) is mounted against the upper cast on the articulator.

Silicone impression is then removed – buccal and labial matrices (surfaces) are replaced. 

Softened wax is then placed in the space for setting the lower teeth for wax try- in.

The Waxed Trial Denture

The soft tissue contours are carefully developed without altering the basic contours of the recorded impression.

The routine assessments are conducted at the trial insertion, with special emphasis on the stability of the denture.

Some other techniques for recording Neutral Zone

Different designs of Impression trays

Injecting the Alginate into the Denture space ‘Impression tray is stabilized by biting’

Articulation & Set-up of teeth

Alginate impression acts as the index for tooth position

Replacing Impression material with Wax rim Setting the teeth with a plaster index

Further Applications of the Basic Technique

Determining the Fit of a completed denture to the Neutral Zone

Coat the polished surfaces of the denture with a low viscosity silicone impression material. Ask the patient to perform functional movements while the material sets. Inspect the denture & adjust any heavy muscle contact.

Determining the optimal space for a segment of the denture

Remove the teeth and the base material from the segment of the denture that needs modification. Apply adhesive and take the impression with moldable material. Check for stability and undertake the laboratory procedures.

Neutral Zone Versus Biometrics

Neutral Zone concept for the placement of artificial teeth could not enjoy the universal approval as did the Biometric concept of tooth arrangement. The reasons for this limited success are numerous, e.g.,

1. The viscosity of the material used for obtaining this impression is critical. More viscous the material, more it will be difficult for the muscles to mold it and visa versa.

2. The geriatric patients could suffer difficulty during the procedure as their musculature may have lost the tone.

3. The stability and retention of the bases on the soft denture support must be excellent as well as the comfort.

4. The resultant ‘neutral zone’ is often narrow and more lingually placed - with the closed mouth technique, the tongue could not perform all the functional movements, such as the phonetics.

5. This technique does not offer any guidelines for the selection of the teeth.

6. The technique is troublesome for the patient and does not offer much advantage over the biometric guides for the arrangement of teeth.